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Novel anti-androgen receptor signaling agents:Understanding the mechanisms of resistance

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Asian Journal of Urology 2014年第1期1卷 30-39页

作者： Styliani Karanika Theodoros Karantanos Jianhua Yin Likun Li timothy c.thompson Department of Genitourinary Medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTXUSA Department of Epidemiology Second Military Medical UniversityShanghaiChina

Prostate cancer remains an intractable threat to the lives of men *** deaths from prostate cancer(Pca)in the United States have declined in recent years,in other parts of the world Pca mortality is *** introduction of 2nd generation antiandrogen receptor agents into the therapeutic armamentarium for metastatic castrationresistant prostate cancer(mcRPc)has resulted in modestly increased survival advantages as demonstrated by initial clinical ***,analysis of the molecular pathways affected by these agents may lead to new insight into mechanisms of resistance that drive mcRPc,including proliferation and survival signaling pathways that are derepressed by maximum repression of androgen *** therapies that involve anti-AR signaling agents together with agents that target these pathways establish a paradigm for the development of more effective treatment of *** this review,we briefly summarize the current clinical trial literature with regard to novel anti-AR signaling agents such as abiraterone acetate and *** discuss observational data that point to mechanisms of resistance that emerged from these *** further present and discuss recent experimental studies that address the mechanisms of resistance to these ***,we discuss novel and rational therapeutic approaches,including combination therapy,for patients with mcRPc.

关键词： Prostate cancer castration-resistant prostate cancer Anti-androgen receptor agents combination therapies

cytopathic effects and local immune responses in repeated neoadjuvant HSV-tk+ ganciclovir gene therapy for prostate cancer

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Asian Journal of Urology 2021年第3期8卷 280-288页

作者： Nobuyuki Yanagisawa Takefumi Satoh Ken-ichi Tabata Hideyasu Tsumura Yasutomo Nasu Masami Watanabe timothy c.thompson Isao Okayasu Yoshiki Murakumo Shiro Baba Masatsugu Iwamura Department of Pathology St.Marianna University School of Medicine Yokohama-City Seibu HospitalYokohamaKanagawaJapan Department of Pathology Kitasato University School of MedicineSagamiharaKanagawaJapan Department of Urology Kitasato University School of MedicineSagamiharaKanagawaJapan Takefumi Satoh Prostate clinic MachidaTokyoJapan Department of Urology Okayama UniversityOkayamaJapan center for Innovative clinical Medicine Okayama University HospitalOkayamaJapan Department of Genitourinary Medical Oncology-Research Division of Cancer MedicineThe University of Texas MD Anderson Cancer CenterHoustonTXUSA Division of Nutrition School of Health CareKiryu UniversityMidori-City GunmaJapan

Objective:cytopathic effects and local immune response were analyzed histologically in prostatic cancer(Pca)with in situ herpes simplex virus-thymidine kinase(HSV-tk)/ganciclovir(GcV)gene therapy(GT).Methods:Four high-risk Pca patients who received HSV-tk/GcV GT were *** two cycles of intraprostatic injection of HSV-tk and administration of GcV,radical prostatectomy was ***-fixed,paraffin-embedded sections were evaluated using *** with hormone therapy(HT,n=3)or without neoadjuvant therapy(NT,n=4)that were equivalent in terms of risk were also examined as ***-positive cells were counted in at least three areas in cancer *** indices(LI)were calculated as percentage ***:ssDNA LI in GT increased,indicating apoptosis,as well as tumor-infiltrating lymphocytes and cD68-positive macrophages,compared with their *** cases showed significantly higher numbers of single-stranded DNA(ssDNA)LI,cD4/cD8-positive T cells and cD68-positive macrophages including M1/M2 macrophages than HT or NT ***,there was no significant difference in cD20-positive B cells among the types of *** were strong correlations between cD8+T cells and cD68+macrophages(ρ=0.656,pcD4+T cells and cD20+B cells(ρ=0.644,pca with ***:Enhanced cytopathic effect and local immune response might be indicated in Pca patients with HSV-tk/GcV gene therapy.

关键词： Suicide genetherapy Prostatecarcinoma HSV-tk Ganciclovir Immuno histochemistry

Follistatin-like protein 1 plays a tumor suppressor role in clear-cell renal cell carcinoma

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cancer communications 2018年第1期38卷 8-22页

作者： Yan Liu Xiaojie Tan Wenbin Liu Xi chen Xiaomei Hou Dan Shen Yibo Ding Jianhua Yin Ling Wang Hongwei Zhang Yongwei Yu Jianguo Hou timothy c.thompson Guangwen cao Department of Epidemiology Second Military Medical UniversityShanghai 200433P.R.China Department of Urology Changhai HospitalSecond Military Medical UniversityShanghai 200433P.R.China Department of Pathology Changhai HospitalSecond Military Medical UniversityShanghai 200433P.R.China Genitourinary Medical Oncology-Research University of Texas MD Anderson Cancer CenterHoustonTX 77030USA

Background:We previously showed that the expression of follistatin-like protein 1(FSTL1)was significantly down-regulated in metastatic clear-cell renal cell carcinoma(ccRcc).In this study,we aimed to characterize the role of FSTL1 in the development of ***:The effects of FSTL1 on cell activity and cell cycle were investigated in ccRcc cell lines with altered FSTL1 *** expression microarray assays were performed to identify the major signaling pathways affected by FSTL1 *** expression of FSTL1 in ccRcc and its effect on postoperative prognosis were estimated in a cohort with 89 ***:FSTL1 knockdown promoted anchorage-independent growth,migration,invasion,and cell cycle of ccRcc cell lines,whereas FSTL1 overexpression attenuated cell ***1 knockdown up-regulated nuclear factor-κB(NF-κB)and hypoxia-inducible factor(HIF)signaling pathways,increased epithelial-to-mesenchymal transition,up-regulated interleukin-6 expression,and promoted tumor necrosis factor-α-induced degradation of NF-κB inhibitor(IκBα)in ccRcc cell ***1 immunostaining was selectively positive in epithelial cytoplasm in the loop of Henle,and positive rate of FSTL1 was significantly lower in ccRcc tissues than in adjacent renal tissues(Pcox regression analysis showed that the intratumoral FSTL1 expression conferred a favorable independent prognosis with a hazard ratio of 0.325(95%confidence interval 0.118-0.894).HIF-2αexpression was negatively cor-related with FSTL1 expression in ccRcc specimens(r=−0.229,P=0.044).Intratumoral expression of HIF-2α,rather than HIF-1α,significantly predicted an unfavorable prognosis in ccRcc(log-rank,P=0.038).conclusions:FSTL1 plays a tumor suppression role possibly via repressing the NF-κB and HIF-2αsignaling *** increase FSTL1 expression might be a candidate therapeutic strategy for metastatic ccRcc.

关键词： Follistatin-like protein 1 clear cell renal cell carcinoma NF-κB HIF-2α Prognosis Tumor suppressor

PI3K/AKT抑制剂Perifosine联合照射治疗前列腺癌

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PI3K/AKT抑制剂Perifosine联合照射治疗前列腺癌

The Impact of the coronavirus Pandemic on the Socioeconomic Future of Young Saudis

中华医学会放射肿瘤治疗学分会六届二次暨中国抗癌协会肿瘤放疗专业委员会二届二次学术会议

作者：高远红王小震 Julie Zhu 麦伟元黄莹 Daniel Floryk Michael Ittmann timothy c.thompson E.Brian Butler Bin S.Teh Department of radiation oncology the Methodist Hospital Department of radiology/radiation oncology Baylor College of Medicine Michael E.DeBakey VA Medical center 华南肿瘤学国家重点实验室中山大学肿防治中心中国医学科学院中国协医科大学肿瘤医院

目的:前列腺在美国是最常见的非上皮性恶性肿瘤,占其男性癌症死因的第二位。放射治疗是前列腺癌重要的治疗手段。新一代的生物反应修饰剂,如以细胞膜为靶点的烷基化磷脂复合物Perifosine,增强了多种恶性肿瘤的放射效应。本研究的目的是...

目的:前列腺在美国是最常见的非上皮性恶性肿瘤,占其男性癌症死因的第二位。放射治疗是前列腺癌重要的治疗手段。新一代的生物反应修饰剂,如以细胞膜为靶点的烷基化磷脂复合物Perifosine,增强了多种恶性肿瘤的放射效应。本研究的目的是探导Perifosine通过抑制PI3K/AKT信号转导通路是否增强了人前列腺癌的放射效应。

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来源： cnki会议评论

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Asian Journal of Middle Eastern and Islamic Studies 2020年第3期14卷 358-382页

作者： Mark c.thompson Socioeconomics Unit King Faisal Center for Research and Islamic StudiesRiyadhSaudi Arabia

The 2020 coronavirus(cOVID-19)pandemic has wreaked havoc with national economies *** Saudi Arabia,the combination of the pandemic’s ramifications coupled with low oil prices had an immediate negative impact on the Saudi economy as well as jeopardising the future plans of many young ***,in a country with approximately 60%of the population under 30 years of age,many of whom are increasingly well-educated,constructive youth engagement is a necessity for the socioeconomic development of Saudi *** fallout from the pandemic could hinder this development as well as exacerbating existing socioeconomic problems for young Saudis,in particular employment *** paper considers to what extent the impact of the pandemic has changed mentalities and attitudes amongst young Saudis towards education,employment,and social *** sum,the paper argues that because of the effect of the coronavirus pandemic on the Saudi socioeconomic environment,a renegotiation of the social contract will be necessary.

关键词： coronavirus pandemic Saudi Arabia Saudi Vision 2030 youth employment social contract

Status and prospects for symmetric organic redox flow batteries

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Journal of Energy chemistry 2025年第1期100卷 125-143页

作者： Md Al Raihan c.Adam Dyker Department of chemistry University of New Brunswick

As environmental concerns from fossil fuel consumption intensify, large-scale energy storage becomes imperative for the integration of renewable sources like wind, hydro, and solar with the electrical *** flow batteries, particularly those employing organic molecules, are positioned as a key technology for this purpose. This review explores the growing field of symmetric organic redox flow batteries(ORFBs) within this context. Unlike traditional asymmetric designs based on unique active materials for each electrode, symmetric ORFBs involve a single bipolar species for both electrodes. This review highlights the benefits of a symmetric design, and categorizes five distinct classes of organic bipolar molecules used in both aqueous and non-aqueous solvents. By providing a comprehensive overview of their cell cycling and performance characteristics, the strengths and weaknesses of the diverse categories of bipolar molecules are highlighted for both solvent systems, as are opportunities for future development. This should guide new research directions and advance the development of practical symmetric ORFBs.

关键词： Redox flow battery Symmetric battery Organic battery Aqueous electrolyte Non-aqueous electrolyte

Acquired sensorineural hearing loss,oxidative stress,and microRNAs

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Neural Regeneration Research 2025年第9期20卷 2513-2519页

作者： Desmond A.Nunez Ru c.Guo Division of Otolaryngology–Head&Neck Surgery Department of SurgeryFaculty of MedicineThe University of British ColumbiaVancouverBCCanada Division of Otolaryngology–Head&Neck Surgery Gordon&Leslie Diamond Health Care CentreVancouver General HospitalVancouverBCCanada Faculty of Medicine–The University of British columbia VancouverBCCanada

Hearing loss is the third leading cause of human ***-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health ***-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing *** etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental *** stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing *** non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic *** hair cell death is a central histopathological finding in sensorineural hearing *** these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing *** EMBASE,Ovid MEDLINE,Web of Science core collection,and *** databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical *** red clinical trials known to the senior author we re also assessed.A total of 222studies were thus *** excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text *** resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative *** miR-34a and miR-29b levels increase with age in *** miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P Gc-1α),SIRT

关键词： hearing loss hypoxia microRNAs oxidative stress sensorineural

Multiple sclerosis is at a checkpoint: advancing the program

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Neural Regeneration Research 2025年第3期20卷 811-812页

作者： Brandon c.Smith Jessica L.Williams Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Biological Geologicaland Environmental SciencesCleveland State UniversityClevelandOHUSA

Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(cNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated b... 详细信息

关键词： Hauser sclerosis damage

Discovery of a pair instability supernova ignites excitement about the first stars

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Science china(Physics,Mechanics & Astronomy) 2023年第9期66卷 198-199页

作者： timothy c.Beers Department of Physics and Astronomy and JINA center for the Evolution of the Elements University of Notre DameNotre Dame 46556USA

For decades,astronomers have predicted that Pair Instability Supernovae(PISNe)might occur when a massive star(140-260 solar masses,M☉)reaches the end of its life,and suffers a cataclysmic explosion due to the transformation of gamma rays in its interior into pairs of free electrons and positrons,robbing the star of the radiation pressure required to support itself against gravity.

关键词： stars massive supernova

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