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The diverse heterogeneity of molecular alterations in prostate cancer identified through next-generation sequencing

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Asian Journal of Andrology 2013年第3期15卷 301-308页

作者： Alexander W Wyatt Fan Mo Yuzhuo Wang colin c collins Vancouver Prostate centre & Department of Urologic Sciences University of British Columbia Vancouver BC V6H 3Z6 Canada Department of Experimental Therapeutics BC Cancer Agency Vancouver BC VSZ 1L3 Canada

Prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity. In recent years, the application of next-generation sequencing to hundreds of prostate tumours has defined novel molecular subtypes and characterized extensive genomic aberration underlying disease initiation and progression. It is now clear that the heterogeneity observed in the clinic is underpinned by a molecular landscape rife with complexity, where genomic rearrangements and rare mutations combine to amplify transcriptomic diversity. This review dissects our current understanding of prostate cancer ＇omics＇, including the sentinel role of copy number variation, the growing spectrum of oncogenic fusion genes, the potential influence of chromothripsis, and breakthroughs in defining mutation-associated subtypes. Increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways, yet recurrent gene aberration appears rare. Therefore, it is critical that we continue to define individual tumour genomes, especially in the context of their expressed transcriptome. Only through improved characterisation of tumour to tumour variability can we advance to an age of precision therapy and personalized oncology.

关键词： cancer sequencing copy number fusion gene genome genome rearrangement personalized oncology prostate cancer transcriptome

The role of mRNA splicing in prostate cancer

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Asian Journal of Andrology 2014年第4期16卷 515-521页

作者： Anna V Lapuk Stanislav V Volik Yuzhuo Wang colin c collins Vancouver Prostate centreUniversity of British columbia Vancouver BC Canada. Department of Experimental Therapeutics BC Cancer AgencyUniversity of British Columbia Vancouver BC Canada. Department of Urologic Sciences University of British Columbia Vancouver BC Canada.

Alternative splicing （AS） is a crucial step in gene expression. It is subject to intricate regulation, and its deregulation in cancer can lead to a wide array of neoplastic phenotypes. A large body of evidence implicates splice isoforms in most if not all hallmarks of cancer, including growth, apoptosis, invasion and metastasis, angiogenesis, and metabolism. AS has important clinical implications since it can be manipulated therapeutically to treat cancer and represents a mechanism of resistance to therapy. In prostate cancer （Pca） AS also plays a prominent role and this review will summarize the current knowledge of alternatively spliced genes with important functional consequences. We will highlight accumulating evidence on AS of the components of the two critical pathways in Pca： androgen receptor （AR） and phosphoinositide 3-kinase （PI3K）. These observations together with data on dysregulation of splice factors in Pca suggest that AR and PI3K pathways may be interconnected with previously unappreciated splicing regulatory networks. In addition, we will discuss several lines of evidence implicating splicing regulation in the development of the castration resistance.

关键词： alternative splicing prostate cancer androgen receptor PI3K pathway cRPc neuroendocrine transdifferentiation REST repressor complex

Prostate cancer metastasis-driving genes： hurdles and potential approaches in their identification

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Asian Journal of Andrology 2014年第4期16卷 545-548页

作者： Yan Ting chiang Peter W Gout colin c collins Yuzhuo Wang The Vancouver Prostate centre Vancouver General Hospital and Department of Urologic Sciences the University of British Columbia Department of Experimental Therapeutics British Columbia Cancer Agency Vancouver British Columbia Canada.

Metastatic prostate cancer is currently incurable. Metastasis is thoughtto result from changes in the expression of specific metastasis-driving genes in nonmetastatic prostate cancer tissue, leading to a cascade of activated downstream genes that set the metastatic process in motion. Such genes could potentially serve as effective therapeutic targets for improved management of the disease. They could be identified by comparative analysis of gene expression profiles of patient-derived metastatic and nonmetastatic prostate cancer tissues to pinpoint genes showing altered expression,

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Next generation patient-derived prostate cancer xenograft models

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Asian Journal of Andrology 2014年第3期16卷 407-412页

作者： Dong Lin Hui Xue Yuwei Wang Rebecca Wu Akira Watahiki Xin Dong Hongwei cheng Alexander W Wyatt colin c collins Peter W Gout Yuzhuo Wang The Vancouver Prostate centre Vancouver Genera Hospital Vancouver Department of Experimental Therapeutics British Columbia Cancer Agency Vancouver Department of Urologic Sciences Faculty of Medicine University of British Columbia Vancouver. British Columbia. Canada.

There is a critical need for more effective therapeutic approaches for prostate cancer. Research in this area, however, has been seriously hampered by a lack of clinically relevant, experimental in vivo models of the disease. This review particularly focuses on the development of prostate cancer xenograft models based on subrenal capsule grafting of patients＇ tumor tissue into nonobese diabetic/ severe combined immunodeficient （NOD/ ScID） mice. This technique allows successful development of transplantable, patient-derived cancer tissue xenograft lines not only from aggressive metastatic, but also from localized prostate cancer tissues. The xenografts have been found to retain key biological properties of the original malignancies, including histopathological and molecular characteristics, tumor heterogeneity, response to androgen ablation and metastatic ability. As such, they are highly clinically relevant and provide valuable tools for studies of prostate cancer progression at cellular and molecular levels, drug screening for personalized cancer therapy and preclinical drug efficacy testing; especially when a panel of models is used to cover a broader spectrum of the disease. These xenograft models could therefore be viewed as next-generation models of prostate cancer.

关键词： effective therapeutic patient-derived xenograft

A practical multi-lane factor model of bridges based on multi-truck presence considering lane load disparities

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Frontiers of Structural and civil Engineering 2021年第4期15卷 877-894页

作者： Junyong ZHOU colin c.cAPRANI School of civil Engineering Guangzhou UniversityGuangzhou510006China Department of civil Engineering Monash UniversityMelbourne3800Australia

Many bridge design specifications consider multi-lane factors(MLFs)a critical component of the traffic load *** multi-lane traffic data generally exhibit significant lane disparities in traffic loads over multiple ***,these disparities are not considered in current *** address this drawback,a multi-coefficient MLF model was developed based on an improved probabilistic statistical approach that considers the presence of multiple *** proposed MLF model and approach were calibrated and demonstrated through an example *** model sensitivity analysis demonstrated the significant influence of lane disparity of truck traffic volume and truck weight distribution on the *** the proposed approach,the experimental site study yielded MLFs comparable with those directly calculated using traffic load *** exclusion of overloaded trucks caused the proposed approach,existing design specifications,and conventional approach of ignoring lane load disparity to generate comparable MLFs,while the MLFs based on the proposed approach were the most *** inclusion of overloaded trucks caused the conventional approach and design specifications to overestimate the MLFs ***,the benefits of the research results to bridge practitioners were discussed.

关键词： bridges multi-lane factor traffic load lane load disparity multi-truck presence weigh-in-motion data

clay mineral records of East Asian monsoon evolution during late Quaternary in the southern South china Sea

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Science china Earth Sciences 2005年第1期48卷 84-92页

作者： c.colin A.Trentesaux D.Blamart FRE 2566 Orsaylerre UMR PBDS du CNRSLaboratoire des Sciences du Climat et de I'Environnement Université de Paris XI91405 OrsayFranceUniversite de Lille I59655 Villeneuve d'AscqFranceLaboratoire mixte CNRS-CEA91198 Gif-sur-YvetteFrance

High-resolution clay mineral records combined with oxygen isotopic stratigraphy over the past 190 ka during late Quaternary from core MD01-2393 off the Mekong River in the southern South china Sea are reported to reconstruct a history of East Asian monsoon *** dominating clay mineral components indicate a strong glacial-interglacial cyclicity, with high glacial illite, chlorite, and kaolinite contents and high interglacial smectites content. The provenance analysis indicates the direct input of clay minerals via the Mekong River drainage *** and chlorite derived mainly from the upper reach of the Mekong River, where physical erosion of meta-sedimentary rocks is dominant. Kaolinite derived mainly from active erosion of inhered clays from reworked sediments in the middle reaches. Smectites originated mainly through bisiallitic soils in the middle to lower reaches of the Mekong River. The smectites/(illite+chlorite)and smectites/kaolinite ratios are determined as mineralogical indicators of East Asian monsoon variations. Relatively high ratios occur during interglacials and indicate strengthened summer-monsoon rainfall and weakened winter-monsoon winds; relatively lower ratios happened in glacials, indicating intensified winter monsoon and weakened summer monsoon. The evolution of the summer and winter monsoons provides an almost linear response to the summer insolation of the Northern Hemisphere, implying an astronomical forcing of the East Asian monsoon evolution.

关键词： clay minerals, East Asian monsoon, late Quaternary, Mekong River, South china Sea.

Integrating volunteered smartphone data with multispectral remote sensing to estimate forest fuels

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International Journal of Digital Earth 2016年第2期9卷 171-196页

作者： colin J.Ferster Nicholas c.coops Department of Forest Resources Management University of British ColumbiaVancouverBCCanada

Volunteered data sources are readily available due to advances in electronic communications *** example,smartphones provide tools to collect ground-based observations over broad areas from a diverse set of data collectors,including people with,and without,extensive *** this study,volunteers used a smartphone application to collect ground-based *** structural components were then estimated over a broader area using high spatial resolution RapidEye remote sensing imagery(5 spectral bands 440–850 nm,5 m spatial resolution)and a digital elevation model following a three nearest neighbor approach(K-NN).Participants with professional forestry experience on average chose highpriority fuel load locations near buildings,while nonprofessional participants chose a broader range of conditions over a larger *** used together,the professional and nonprofessional observations provided a more complete assessment of forest conditions.A generalized framework is presented that utilizes K-NN imputation tools for estimating the distribution of forest fuels using remote sensing and topography variables,ensuring spatial representation,checking attribute accuracy,and evaluating predictor *** to integrate volunteered data from smartphone platforms with remote sensing may contribute toward more complete Earth observation for Digital Earth.

关键词： citizen science public participation in scientific research mobile RapidEye red edge WUI

Pilot plants of membrane technology in industry:challenges and key learnings

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Frontiers of chemical Science and Engineering 2020年第3期14卷 305-316页

作者： colin A.Scholes Peter cook centre for carbon capture and Storage Research Department of Chemical EngineeringThe University of MelbourneVIC3010Australia

Membrane technology holds great potential in gas separation applications,especially carbon dioxide capture from industrial *** achieve this potential,the outputs from global research endeavours into membrane technologies must be trialled in industrial processes,which requires membrane-based pilot *** pilot plants are critical to the commercialization of membrane technology,be it as gas separation membranes or membrane gas-solvent contactors,as failure at the pilot plant level may delay the development of the technology for ***,the author reports on his experience of operating membrane-based pilot plants for gas separation and contactor configurations as part of three industrial carbon capture initiatives:the Mulgrave project,H3 project and Vales Point ***,the challenges of developing and operating membrane pilot plants are presented,as well as the key learnings on how to successfully manage membrane pilot plants to achieve desired performance *** purpose is to assist membrane technologists in the carbon capture field to achieve successful outcomes for their technology innovations.

关键词： membrane gas separation membrane contactors carbon capture pilot plants key learnings

Molecular targets in the treatment of alcoholic hepatitis

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World Journal of Gastroenterology 2012年第39期18卷 5504-5513页

作者： Ashwin D Dhanda Richard WL Lee Peter L collins c Anne Mccune Department of Liver Medicine University Hospitals Bristol NHS Foundation TrustBS2 8HW BristolUnited Kingdom Department of cellular and Molecular Medicine School of Clinical SciencesUniversity of BristolBS9 1TD BristolUnited Kingdom

Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, cXcL9 and cXcR3) and augmentation of anti-inflam- matory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease.

关键词： Alcoholic hepatitis Tumour necrosis factor-m Pentoxifylline Interleukins chemokine receptors