Yuzhuo Wang

Professor

Research Classification

Prostate Cancer

Research Interests

Modeling and Targeting the Development of Castration-Resistant Prostate Cancer

Relevant Degree Programs

 

Biography

Dr. Yuzhuo Wang, Ph.D. FCAHS (王玉琢院士) has a dual appointment as a Distinguished Scientist at the BC Cancer Research Centre and Senior Research Scientist at the Vancouver Prostate Centre. He is also the Founder of the Living Tumor Laboratory (www.livingtumorlab.com) and a Professor in Department of Urologic Sciences at UBC. Dr. Wang did his Ph.D. at the University of Hong Kong, and joined Dr. Gerald R. Cunha at University of California, San Francisco (UCSF) as a postdoctoral fellow in 1997. Since then, He has authored/co-authored over 150 peer reviewed articles, many in top-tier journals such as Cancer Research, Cancer Cell, Nature Medicine, Nature, Clinical Cancer Research, and European Urology. He has published 13 book chapters and edited two books (i.e. PDX Model of Human Cancers and Tumor Dormancy). As a principal investigator, he is well funded by a number of agencies (e.g., the Canadian Institutes of Health Research).
Dr. Wang’s academic contributions can be highlighted by a number of novel hypotheses he has proposed, such as hypotheses on “prostate stem cells”, “epithelial-immune cell transition (EIT)”, “cancer-generated lactic acid is critical, immunosuppressive metabolite rather than a ‘waste product’ (which has been believed for more than 90 years)” and “tumour dormancy is a non-genetic disease”. Dr. Wang is recognized for his pioneering work in the field of prostate cancer modeling. He was the first to establish tissue recombination model of hormonal prostatic carcinogenesis. He also developed the first model of hormonal carcinogenesis in human prostatic epithelium. Moreover, he is responsible for a novel method for establishing transplantable, patient-derived xenograft models that closely resemble patients’ malignancies. Using the methodology, his group has developed over 300 transplantable patient-derived xenograft models in the Living Tumor Laboratory. Importantly such “next generation” xenograft models have been effectively applied in a number of research areas, such as (i) preclinical drug efficacy studies in anti-cancer therapeutics development, (ii) discovery and validation of potential biomarkers and/or therapeutic targets, and (iii) personalized cancer therapy.
Dr. Wang has received numerous awards for his academic achievements in cancer research, such as a Prostate Cancer Foundation Research Award (2007), the Translation Research Award from Roche (2009), an Overseas Chinese Scholars Award from the National Natural Science Foundation of China (2009), the Innovative Scholar Award from the International Cancer Alliance for Research and Education (ICARE), US (2010), an UBC Faculty of Medicine Distinguished Achievement Award (2011), an UBC Department of Urologic Sciences Outstanding Academic Performance Award (2013) and a Department of Urologic Sciences Research Teaching Excellence Award (2015), and an UBC Department of Urologic Sciences Outstanding Academic Performance Award (2017). Notably, he has been inducted as a Fellow of the Canadian Academy of Health Sciences (FCAHS) (加拿大健康科学院院士) in 2018.

Research Methodology

PDX models
Target discovery
Drug development

Recruitment

Doctoral students
Postdoctoral Fellows
Any time / year round
I support public scholarship, e.g. through the Public Scholars Initiative, and am available to supervise students and Postdocs interested in collaborating with external partners as part of their research.
I support experiential learning experiences, such as internships and work placements, for my graduate students and Postdocs.
I am open to hosting Visiting International Research Students (non-degree, up to 12 months).

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Graduate Student Supervision

Doctoral Student Supervision (Jan 2008 - Nov 2019)
Potential use of Aneustat for improvement of docetaxel-based therapy of advanced prostate cancer (2018)

Metastatic prostate cancer (mPCa) is currently incurable. Docetaxel-based chemotherapy, used as first-line treatment for advanced PCa, is marginally effective. As PCa is a heterogeneous disease, use of therapeutics targeting multiple pathways may improve its treatment outcome. Aneustat is first-of-a-class of multivalent immuno-oncology drug candidates; a Phase-I trial has shown it is well-tolerated by patients and has immunomodulatory activity. The main goal of this PhD project is to determine whether Aneustat can be used to improve docetaxel-based therapy of advanced PCa. In vitro, Aneustat markedly inhibited human metastatic C4-2 PCa cell proliferation/migration in a dose-dependent manner and, combined with docetaxel, showed synergistic growth inhibition. In vivo, a combination of Aneustat and docetaxel synergistically enhanced anticancer activity in a clinically relevant, patient-derived xenograft (PDX) metastatic PCa model without inducing major host toxicity (inhibition of tumor growth, lung micro-metastasis, kidney invasion). Gene expression analysis of microarray data obtained from xenografts, using Ingenuity Pathway Analysis (IPA) and Oncomine software, indicated that Aneustat+docetaxel, as distinct from the single drugs, targeted multiple pathways and cancer-driving genes. Aneustat alone significantly inhibited growth of human LNCaP cells/xenografts; glucose consumption, lactic acid secretion and glycolysis-related gene expressions of LNCaP cells were markedly reduced, indicating it inhibited aerobic glycolysis. Treatment of LNCaP xenografts and first-generation PCa PDX with Aneustat led to marked changes in host immune cell levels (mouse/human), i.e. a higher ratio of CD8⁺T/Treg cells, higher Natural Killer (NK) cell numbers, lower Treg cell and MDSC numbers – changes favoring the host anticancer immune response. This study shows that combined use of Aneustat and docetaxel can lead to marked, synergistically increased anticancer activity, both in vitro and in vivo. As indicated by IPA and Oncomine analyses, this is due to the combination-induced expansion of the targeting of pathways and cancer-driving genes. Furthermore, as found with first-generation PDX PCa model, Aneustat has immunomodulatory properties, likely stemming from its inhibition of aerobic glycolysis, that may lead to stimulation of the anticancer immune response in immunocompetent hosts. Since a clinically relevant PDX metastatic PCa model was used in this study, treatment with Aneustat+docetaxel is likely valuable for clinical management of advanced PCa.

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Targeting MCT4 for treatment of advanced prostate cancers : inhibiting cell proliferation and enhancing anticancer immunity through suppressing lactic acid secretion and elevated glycolysis (2018)

Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer in North American males and a leading cause of cancer deaths. The lack of effective treatment options for advanced PCa such as AR-positive castration-resistant PCa (CRPC-AD) and the highly aggressive AR-negative CRPC, e.g. neuroendocrine PCa (CRPC-NE) presents a critical, unmet need for the development of novel therapeutics. Altered metabolism in the form of elevated aerobic glycolysis is a common cancer characteristic. Here we propose a novel conceptual understanding for the central, functional role of excessive cancer-generated lactic acid. In particular, the acidification of the tumor microenvironment via increased MCT4-mediated lactic acid secretion can facilitate multiple crucial cancer-promoting processes, including proliferation, tissue invasion/metastasis, angiogenesis, and suppression of local anticancer immunity. As such, the inhibition of MCT4 could be an effective therapeutic strategy broadly impacting multiple downstream lactate-associated tumour-promoting processes. Experimentally, we were able to confirm the clinical relevance of elevated glycolysis and increased lactic acid production in various advanced PCa patient-derived xenograft (PDX) models and patient tumours using a novel metabolic pathway score. In particular, NEPC tumours appear to rely much more heavily on elevated aerobic glycolysis and MCT4-mediated lactic acid secretion. In a proof-of-concept study using MCT4-specific antisense oligonucleotides (ASOs), reduced MCT4 expression is able to reduce proliferation, invasion/migration, and glucose metabolism of advanced PCa cells in vitro. More importantly, we demonstrated in two distinct in vivo models containing residual functional immune cells that MCT4 inhibition enhanced anticancer immunity. Finally, a state-of-the-art in silico drug discovery pipeline was employed in the first steps towards developing a potent and specific MCT4 small molecule inhibitor. Computer modeling of MCT4 structure, virtual molecular docking, and downstream experimental validation identified a promising hit series based on the chemical scaffold of VPC-25009 as a potential second therapeutic modality for MCT4 inhibition. Taken together, we were able to provide experimental support for our novel hypothesis regarding the central tumour-promoting and immunosuppressive role of cancer-generated lactic acid. A therapeutic approach blocking lactic acid secretion by targeting MCT4 function could thus inhibit multiple downstream lactate-associated processes for effective treatment of advanced PCa and other highly glycolytic cancers.

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BIRC6 as novel therapeutic target in advanced prostate cancer : clinical relevance, development of potential therapeutic agents & preclinical drug efficacy (2016)

The lack of effective therapy for advanced prostate cancer (PCa) remains a major unmet clinical need. Recently approved therapeutics, such as enzalutamide (ENZ), have only delayed the inevitable progression of castration-resistant PCa (CRPC), as resistance will typically emerge following treatment. Although increased apoptosis-resisting ability of cancer cells represents a fundamental mechanism for the onset of treatment resistance, no relevant agents have yet been developed. Preliminary work in our laboratory has revealed an association between elevated expression of BIRC6, an Inhibitor of Apoptosis (IAP) protein, and advanced PCa. The overall objective of this doctoral study is to investigate the roles of BIRC6 in advanced PCa, and to assess the therapeutic efficacy of a novel anti-BIRC6 agent. Firstly, I evaluated the clinical relevance of BIRC6 using patients’ PCa specimens, and the functional importance of BIRC6 using cell line-based PCa models. A significant correlation was found between elevated BIRC6 protein expression in clinical PCa and poor patient prognostic factors. Functional assays validated the importance of BIRC6 in PCa cell proliferation and apoptosis suppression. Next, I designed BIRC6-based, dual IAP-targeting antisense oligonucleotides (dASOs) to inhibit BIRC6 and an additional IAP. Two dASOs, 6w2 and 6w5 targeting BIRC6+cIAP1 and BIRC6+survivin, showed substantial inhibition of CRPC cell proliferation in vitro and in vivo. Functional studies showed that both dASOs significantly induced apoptosis, cell cycle arrest and suppression of NFκB activation in CRPC cells. Finally, I assessed the growth-inhibitory efficacy of dASO-6w2 in ENZ-resistant CRPC, which has become an increasingly prominent problem in the clinic. The efficacy of dASO-6w2 was studied using both ENZ-resistant PCa cell lines and a clinically relevant, transplantable patient-derived xenograft PCa tissue model, designated LTL-313BR, which exhibits primary ENZ resistance. Importantly, I showed that treatment with dASO-6w2 markedly suppressed the growth of LTL-313BR xenografts. The dASO-6w2 was also found to increase tumour apoptosis and inhibit the expression of several pro-survival genes that were up-regulated in the LTL-313BR line. In conclusion, this doctoral study has established the clinical relevance and functional importance of BIRC6 in advanced PCa, and has also presented new BIRC6-targeting agents that markedly suppress the growth of advanced PCa.

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Identification of metastasis-driving genes as potential therapeutic targets/ biomarkers for metastatic prostate cancer (2015)

Metastatic prostate cancer is currently incurable. Metastasis is thought to result from changes in the expression of specific metastasis-driving genes, leading to a cascade of activated downstream genes setting the metastatic process in motion. As such, metastasis-driving genes could provide effective therapeutic targets and prognostic biomarkers for improved disease management. In search of potential metastasis-driving genes, genes with elevated expression in patient-derived metastatic LTL-313H prostate cancer tissues, as distinct from non-metastatic LTL-313B tissues, were identified. Among these genes, TIMELESS and DLX1 were promising. Unfortunately, their silencing and overexpression in prostate cancer cells did not lead to inhibition of metastatic properties, indicating that they were not metastasis-driving genes. A different, novel approach was used based on the notion that metastasis-driving genes can activate genes in an amplification cascade fashion. Accordingly, I used the IPA’s Upstream Regulator Analysis tool to analyze the differential gene expression profile of the metastatic and non-metastatic tissues to predict the upstream master regulatory (metastasis-driving) genes accountable for the differential expression. Six candidate genes were identified, including GATA2, a pioneer factor-encoding gene. Elevated GATA2 expression in clinical metastatic prostate cancer specimens correlated with poor patient prognosis. Furthermore, GATA2 gene silencing in human prostate cancer LNCaP cells led to marked reduction in cell proliferation, cell migration, tissue invasion, focal adhesion disassembly and a dramatic change in transcriptional activity, indicating that GATA2 plays a critical role in prostate cancer metastasis. As such, GATA2 could represent a metastasis-driving gene and a potential therapeutic target for inhibiting the growth and metastasis development in prostate cancer. Further analysis of GATA2-regulated genes led to the development of a GATA2-based metastatic gene signature. Its prognostic value was confirmed using two prostate cancer patient cohorts. In addition, it was shown to be a prognostic factor for risk assessment of metastasis development, independent of the widely used D’Amico prognostic classification system. However, a thorough validation is critical and, if successful, the GATA2-based gene signature could lead to a paradigm shift in the management of early prostate cancer. In conclusion, the findings of this study appear to be potentially useful for improved management of metastatic prostate cancer.

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Tumor-promoting effects on Genistein and ER beta prostate cancer (2012)

No abstract available.

Publications

  • A synopsis of prostate organoid methodologies, applications, and limitations (2020)
    The Prostate,
  • Well-Differentiated Papillary Mesothelioma of the Peritoneum is Genetically Distinct from Malignant Mesothelioma (2019)
  • A heterochromatin gene signature unveils HP1$α$ mediating neuroendocrine prostate cancer development and aggressiveness (2018)
  • Aneustat (OMN54) has aerobic glycolysis-inhibitory activity and also immunomodulatory activity as indicated by a first-generation PDX prostate cancer model (2018)
    International Journal of Cancer, 143 (2), 419--429
  • BAP1 Loss Predicts Therapeutic Vulnerability in Malignant Peritoneal Mesothelioma (2018)
    bioRxiv, , 243477
  • Copy number estimation from whole-exome sequencing in tumors (2018)
  • Inhibition of Transient Receptor Potential Vanilloid 6 channel, elevated in human ovarian cancers, reduces tumour growth in a xenograft model (2018)
    Journal of Cancer, 9 (17), 3196--3207
  • Is HOTAIR really involved in neuroendocrine prostate cancer differentiation? (2018)
  • Movember GAP1 PDX project: An international collection of serially transplantable prostate cancer patient-derived xenograft (PDX) models (2018)
    The Prostate,
  • Neuroendocrine differentiation of prostate cancer leads to PSMA suppression (2018)
    Endocrine-Related Cancer, 1 (aop)
  • Patient-derived hormone-naive prostate cancer xenograft models reveal GRB10 as an AR-repressed gene driving the development of castration-resistant prostate cancer (2018)
  • Pre-clinical Models for Malignant Mesothelioma Research: From Chemical-induced to Patient-derived Cancer Xenografts (2018)
    Frontiers in Genetics, 9, 232
  • Prevention of Prostate Tumor Development by Stimulation of Antitumor Immunity Using a Standardized Herbal Extract (Deep Immune®) in TRAMP Mice (2018)
    Evidence-Based Complementary and Alternative Medicine,
  • Proteogenomic characterization of patient-derived xenografts highlights the role of REST in neuroendocrine differentiation of castration-resistant prostate cancer (2018)
    Clinical Cancer Research, , clincanres--0729
  • Selective inhibition of the lactate transporter MCT4 reduces growth of invasive bladder cancer (2018)
    Molecular Cancer Therapeutics, , molcanther--0107
  • TMEM45B is a novel predictive biomarker for prostate cancer progression and metastasis. (2018)
    Neoplasma, 65 (5), 815--821
  • A germline FANCA alteration that is associated with increased sensitivity to DNA damaging agents (2017)
    Molecular Case Studies, , mcs--a001487
  • Androgen receptor transcriptionally regulates semaphorin 3C in a GATA2-dependent manner (2017)
    Oncotarget, 8 (6), 9617
  • BIRC6 Targeting as Potential Therapy for Advanced, Enzalutamide-Resistant Prostate Cancer (2017)
    Clinical Cancer Research, 23 (6), 1542--1551
  • Dual targeting antisense oligonucleotides as apoptotic inhibtor therapeutic compostions and methods for their use in the treatment of cancer (2017)
  • Hormonal Carcinogenesis: The Role of Estrogens (2017)
    The Molecular Basis of Human Cancer, , 307--322
  • Metabolic heterogeneity signature of primary treatment-näıve prostate cancer (2017)
    Oncotarget, 8 (16), 25928
  • Patient-derived xenografts: A platform for accelerating translational research in prostate cancer (2017)
    Molecular and Cellular Endocrinology,
  • SRRM4 drives neuroendocrine transdifferentiation of prostate adenocarcinoma under androgen receptor pathway inhibition (2017)
    European urology, 71 (1), 68--78
  • Stromal Gene Expression is Predictive for Metastatic Primary Prostate Cancer (2017)
    European Urology,
  • The Master Neural Transcription Factor BRN2 Is an Androgen Receptor--Suppressed Driver of Neuroendocrine Differentiation in Prostate Cancer (2017)
    Cancer discovery, 7 (1), 54--71
  • An Aqueous Extract of Marine Microalgae Exhibits Antimetastatic Activity through Preferential Killing of Suspended Cancer Cells and Anticolony Forming Activity (2016)
    Evidence-Based Complementary and Alternative Medicine, 2016
  • BPS-001, a complex biologic agent extracted from the medicinal leech (Huridinaria manillensis) for treatment of metastatic castration-resistant prostate cancer. (2016)
  • Diffuse large B-cell lymphoma patient-derived xenograft models capture the molecular and biological heterogeneity of the disease (2016)
    Blood, 127 (18), 2203--2213
  • Elevated expression of the centromere protein-A (CENP-A)-encoding gene as a prognostic and predictive biomarker in human cancers (2016)
    International journal of cancer, 139 (4), 899--907
  • Identification of the epigenetic reader CBX2 as a potential drug target in advanced prostate cancer (2016)
    Clinical epigenetics, 8 (1), 16
  • Immune phenotypes of prostate cancer cells: Evidence of epithelial immune cell-like transition? (2016)
    Asian Journal of Urology, 3 (4), 195--202
  • Integrated analysis of the prostate cancer small-nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression (2016)
    Molecular oncology, 10 (5), 693--703
  • MP61-03 EVALUATION OF LACTATE TRANSPORTERS AS POTENTIAL THERAPEUTIC TARGET IN UROTHELIAL CARCINOMA (2016)
    The Journal of Urology, 195 (4), e804
  • Semaphorin 3C is an androgen receptor-regulated gene (2016)
  • Subrenal capsule grafting technology in human cancer modeling and translational cancer research (2016)
    Differentiation, 91 (4), 15--19
  • Switching off malignant mesothelioma: exploiting the hypoxic microenvironment (2016)
    Genes & cancer, 7 (11-12), 340
  • The MCT4 gene: a novel, potential target for therapy of advanced prostate cancer (2016)
    Clinical Cancer Research, 22 (11), 2721--2733
  • The role of epigenetics and long noncoding RNA MIAT in neuroendocrine prostate cancer (2016)
  • Androgen receptor gene aberrations in circulating cell-free DNA: biomarkers of therapeutic resistance in castration-resistant prostate cancer (2015)
    Clinical cancer research, 21 (10), 2315--2324
  • Animal Models of Metastasis (2015)
    Genomic Instability and Cancer Metastasis, , 95--123
  • Diffuse Large B-Cell Lymphoma Patient-Derived Xenograft Models Capture Molecular and Biologic Heterogeneity and Inform Therapy (2015)
  • Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution (2015)
    Nature, 518 (7539), 422
  • Generation 2.5 antisense oligonucleotides targeting the androgen receptor and its splice variants suppress enzalutamide-resistant prostate cancer cell growth (2015)
    Clinical cancer research, 21 (7), 1675--1687
  • Identification and functional characterization of a long non-coding RNA driving hormone-independent prostate cancer progression. (2015)
  • Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer (2015)
    Oncotarget, 6 (3), 1806
  • miR-188-5p inhibits tumour growth and metastasis in prostate cancer by repressing LAPTM4B expression (2015)
    Oncotarget, 6 (8), 6092
  • Molecular and pathological characterization of the EZH2 rs3757441 single nucleotide polymorphism in colorectal cancer (2015)
    BMC cancer, 15 (1), 874
  • Patient-derived bladder cancer xenografts in the preclinical development of novel targeted therapies (2015)
    Oncotarget, 6 (25), 21522
  • Polycomb genes are associated with response to imatinib in chronic myeloid leukemia (2015)
    Epigenomics, 7 (5), 757--765
  • Polycomb-mediated silencing in neuroendocrine prostate cancer (2015)
    Clinical epigenetics, 7 (1), 40
  • The epigenetic/noncoding origin of tumor dormancy (2015)
    Trends in molecular medicine, 21 (4), 206--211
  • The expression of glucocorticoid receptor is negatively regulated by active androgen receptor signaling in prostate tumors (2015)
    International journal of cancer, 136 (4)
  • The long non-coding RNA PCGEM1 is regulated by androgen receptor activity in vivo (2015)
    Molecular cancer, 14 (1), 46
  • The Non-Coding Transcriptome as a Dynamic Regulator of Prostate Cancer Metastasis (2015)
    The FASEB Journal, 29 (1 Sup), 221--3
  • The placental gene PEG10 promotes progression of neuroendocrine prostate cancer (2015)
    Cell reports, 12 (6), 922--936
  • Translational activation of HIF1$α$ by YB-1 promotes sarcoma metastasis (2015)
    Cancer cell, 27 (5), 682--697
  • Whole-exome sequencing of metastatic cancer and biomarkers of treatment response (2015)
    JAMA oncology, 1 (4), 466--474
  • YB-1 regulates stress granule formation and tumor progression by translationally activating G3BP1 (2015)
    J Cell Biol, , jcb--201411047
  • 403 Patient-derived primary xenografts in the preclinical development of novel targeted therapies for bladder cancer (2014)
    European Urology Supplements, 13 (1), e403
  • A meta-analysis approach for characterizing pan-cancer mechanisms of drug sensitivity in cell lines (2014)
    PloS one, 9 (7), e103050
  • Crosstalk between nuclear MET and SOX9/$β$-catenin correlates with castration-resistant prostate cancer (2014)
    Molecular Endocrinology, 28 (10), 1629--1639
  • Crosstalk Between Nuclear MET and SOX9/ß-Catenin Correlates with Castration-Resistant Prostate Cancer (2014)
  • Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patient-derived, advanced prostate cancer tissue xenograft model (2014)
    Molecular oncology, 8 (2), 311--322
  • GATA2 as a potential metastasis-driving gene in prostate cancer (2014)
    Oncotarget, 5 (2), 451
  • GATA2: Potential role as a prostate cancer metastasis-driving gene (2014)
  • Heterogeneity in the inter-tumor transcriptome of high risk prostate cancer (2014)
    Genome biology, 15 (8), 426
  • High fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development (2014)
    Cancer research, 74 (4), 1272--1283
  • Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer (2014)
    Oncotarget, 5 (3), 764
  • INPP4B suppresses prostate cancer cell invasion (2014)
    Cell Communication and Signaling, 12 (1), 61
  • Lessons from patient-derived xenografts for better in vitro modeling of human cancer (2014)
    Advanced drug delivery reviews, 79, 222--237
  • MP31-09 IDENTIFICATION OF A RETRO-TRANSPOSON DERIVED GENE ASSOCIATED WITH PROGRESSION TO NEUROENDOCRINE PROSTATE CANCER. (2014)
    The Journal of Urology, 191 (4), e325
  • Next generation patient-derived prostate cancer xenograft models (2014)
    Asian journal of andrology, 16 (3), 407
  • Patient-derived Xenografts For Accelerating Prostate Cancer Discovery And Drug Development (2014)
    International Journal of Urology, 21, A45
  • Prostate cancer metastasis-driving genes: hurdles and potential approaches in their identification (2014)
    Asian journal of andrology, 16 (4), 545
  • Systematic identification and characterization of RNA editing in prostate tumors (2014)
    PloS one, 9 (7), e101431
  • The BIRC6 gene as a novel target for therapy of prostate cancer: dual targeting of inhibitors of apoptosis (2014)
    Oncotarget, 5 (16), 6896
  • The non-coding transcriptome as a dynamic regulator of cancer metastasis (2014)
    Cancer and Metastasis reviews, 33 (1), 1--16
  • The role of mRNA splicing in prostate cancer (2014)
    Asian journal of andrology, 16 (4), 515
  • BIRC6 protein, an inhibitor of apoptosis: role in survival of human prostate cancer cells (2013)
    PLoS one, 8 (2), e55837
  • Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite? (2013)
    The Journal of pathology, 230 (4), 350--355
  • Chromoplexy: a new paradigm in genome remodeling and evolution (2013)
    Asian journal of andrology, 15 (6), 711
  • Deletion of leucine zipper tumor suppressor 2 (lzts2) increases susceptibility to tumor development (2013)
    Journal of Biological Chemistry, 288 (6), 3727--3738
  • Developmental and androgenic regulation of chromatin regulators EZH2 and ANCCA/ATAD2 in the prostate Via MLL histone methylase complex (2013)
    The Prostate, 73 (5), 455--466
  • Elevated expression of BIRC6 protein in non--small-cell lung cancers is associated with cancer recurrence and chemoresistance (2013)
    Journal of Thoracic Oncology, 8 (2), 161--170
  • ERBB4 confers metastatic capacity in Ewing sarcoma (2013)
    EMBO molecular medicine, 5 (7), 1087--1102
  • Expression and function of the progesterone receptor in human prostate stroma provide novel insights to cell proliferation control (2013)
    The Journal of Clinical Endocrinology & Metabolism, 98 (7), 2887--2896
  • Genistein versus ICI 182, 780: an ally or enemy in metastatic progression of prostate cancer (2013)
    The Prostate, 73 (16), 1747--1760
  • Lessons from in-vivo models of castration-resistant prostate cancer (2013)
    Current opinion in urology, 23 (3), 214--219
  • Plasma miRNAs as biomarkers to identify patients with castration-resistant metastatic prostate cancer (2013)
    International journal of molecular sciences, 14 (4), 7757--7770
  • Prognostication of prostate cancer based on NUCB2 protein assessment: NUCB2 in prostate cancer (2013)
    Journal of Experimental & Clinical Cancer Research, 32 (1), 77
  • REST mediates androgen receptor actions on gene repression and predicts early recurrence of prostate cancer (2013)
    Nucleic acids research, 42 (2), 999--1015
  • The diverse heterogeneity of molecular alterations in prostate cancer identified through next-generation sequencing (2013)
    Asian journal of andrology, 15 (3), 301
  • A versatile monoclonal antibody specific to human SERPINB5 (2012)
    Hybridoma, 31 (5), 333--339
  • Androgen hormone action in prostatic carcinogenesis: stromal androgen receptors mediate prostate cancer progression, malignant transformation and metastasis (2012)
    Carcinogenesis, 33 (7), 1391--1398
  • Drug sensitivity testing for personalized lung cancer therapy (2012)
    Journal of thoracic disease, 4 (1), 17
  • Epithelial immune cell-like transition (EIT): a proposed transdifferentiation process underlying immune-suppressive activity of epithelial cancers (2012)
    Differentiation, 83 (5), 293--298
  • From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancer (2012)
    The Journal of pathology, 227 (3), 286--297
  • Increased PrLZ-mediated androgen receptor transactivation promotes prostate cancer growth at castration-resistant stage (2012)
    Carcinogenesis, 34 (2), 257--267
  • Integrin-linked kinase as a target for ERG-mediated invasive properties in prostate cancer models (2012)
    Carcinogenesis, 33 (12), 2558--2567
  • Next generation sequencing of prostate cancer from a patient identifies a deficiency of methylthioadenosine phosphorylase, an exploitable tumor target (2012)
    Molecular cancer therapeutics, 11 (3), 775--783
  • Poly-gene fusion transcripts and chromothripsis in prostate cancer (2012)
    Genes, Chromosomes and Cancer, 51 (12), 1144--1153
  • Collagen triple helix repeat containing 1 promotes melanoma cell adhesion and survival (2011)
    Journal of cutaneous medicine and surgery, 15 (2), 103--110
  • Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells (2011)
    Blood, 118 (12), 3350--3358
  • CSF1 expression in nongynecological leiomyosarcoma is associated with increased tumor angiogenesis (2011)
    The American journal of pathology, 179 (4), 2100--2107
  • Genistein increases epidermal growth factor receptor signaling and promotes tumor progression in advanced human prostate cancer (2011)
    PloS one, 6 (5), e20034
  • Identification of novel therapeutic targets in microdissected clear cell ovarian cancers (2011)
    PloS one, 6 (7), e21121
  • Immunohistochemical expression of neurotrophic tyrosine kinase receptors 1 and 2 in lung carcinoma: potential discriminators between squamous and nonsquamous subtypes (2011)
    Archives of pathology & laboratory medicine, 135 (4), 433--439
  • MicroRNAs associated with metastatic prostate cancer (2011)
    PloS one, 6 (9), e24950
  • Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets (2011)
    Cancer discovery, 1 (6), 487--495
  • Multiplexed quantum dot labeling of activated c-Met signaling in castration-resistant human prostate cancer (2011)
    PloS one, 6 (12), e28670
  • Optimally discriminative subnetwork markers predict response to chemotherapy (2011)
    Bioinformatics, 27 (13), i205--i213
  • Quantum Dot Multispectral Imaging Detects Cell Signaling for Prostate Cancer Progression (2011)
    EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, 40, 65--66
  • The immunoregulatory mechanisms of carcinoma for its survival and development (2011)
    Journal of Experimental & Clinical Cancer Research, 30 (1), 12
  • Use of irinotecan for treatment of small cell carcinoma of the prostate (2011)
    The Prostate, 71 (7), 675--681
  • A panel of new patient-derived melanoma xenograft models (2010)
    Pigment Cell & Melanoma Research, 23 (5), 719
  • Cell biology of prostate cancer and molecular targets (2010)
    Drug Management of Prostate Cancer, , 1--24
  • Development of metastatic and non-metastatic tumor lines from a patient's prostate cancer specimen—identification of a small subpopulation with metastatic potential in the primary tumor (2010)
    The Prostate, 70 (15), 1636--1644
  • Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails (2010)
    Oncogene, 29 (25), 3593--3604
  • Estrogen receptor--$β$ activated apoptosis in benign hyperplasia and cancer of the prostate is androgen independent and TNF$α$ mediated (2010)
    Proceedings of the National Academy of Sciences, 107 (7), 3123--3128
  • Induction of neuronal apoptosis inhibitory protein expression in response to androgen deprivation in prostate cancer (2010)
    Cancer letters, 292 (2), 176--185
  • Patient-derived first generation xenografts of non--small cell lung cancers: promising tools for predicting drug responses for personalized chemotherapy (2010)
    Clinical Cancer Research, 16 (5), 1442--1451
  • Potential use of the anti-inflammatory drug, sulfasalazine, for targeted therapy of pancreatic cancer (2010)
    Current oncology, 17 (3), 9
  • Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor (2010)
    Cancer cell, 17 (6), 535--546
  • Therapeutic antibodies targeting CSF1 impede macrophage recruitment in a xenograft model of tenosynovial giant cell tumor (2010)
    Sarcoma, 2010
  • Tumor growth inhibition by olaparib in BRCA2 germline-mutated patient-derived ovarian cancer tissue xenografts (2010)
    Clinical Cancer Research, , clincanres--1382
  • A novel protein isoform of the multicopy human NAIP gene derives from intragenic Alu SINE promoters (2009)
    PloS one, 4 (6), e5761
  • Abstract# 4183: Proposed epithelial-immune cell transition (EIT) of cancer cells may be critical for survival of prostate cancers via evasion of immune surveillance (2009)
  • Inhibition of the androgen receptor as a novel mechanism of taxol chemotherapy in prostate cancer (2009)
    Cancer research, 69 (21), 8386--8394
  • Proposed epithelial-immune cell transition (EIT) of cancer cells may be critical for survival of prostate cancers via evasion of immune surveillance (2009)
    CANCER RESEARCH, 69
  • Response to Savaskan NE et al.“The x c- cystine/glutamate antiporter—A potential target for therapy of cancer and other diseases: Yet another cytotoxic anticancer approach?” (2009)
    Journal of Cellular Physiology, 220 (2), 533--534
  • Selective elevation of adiponectin production by the natural compounds derived from a medicinal herb alleviates insulin resistance and glucose intolerance in obese mice (2009)
    Endocrinology, 150 (2), 625--633
  • The xc- cystine/glutamate antiporter as a potential therapeutic target for small-cell lung cancer: use of sulfasalazine (2009)
    Cancer chemotherapy and pharmacology, 64 (3), 463
  • ASAP1, a gene at 8q24, is associated with prostate cancer metastasis (2008)
    Cancer research, 68 (11), 4352--4359
  • Decitabine-induced demethylation of 5′ CpG island in GADD45A leads to apoptosis in osteosarcoma cells (2008)
    Neoplasia, 10 (5), 471--480
  • ERG expression is sufficient to induce epithelial-to-mesenchymal transition and transform prostatic epithelial cells. (2008)
  • Prostatic hormonal carcinogenesis is mediated by in situ estrogen production and estrogen receptor alpha signaling (2008)
    The FASEB journal, 22 (5), 1512--1520
  • The x cystine/glutamate antiporter: A potential target for therapy of cancer and other diseases (2008)
    Journal of cellular physiology, 215 (3), 593--602
  • The xc- cystine/glutamate antiporter: a mediator of pancreatic cancer growth with a role in drug resistance (2008)
    British journal of cancer, 99 (3), 464--472
  • The xc-cystine transporter as a target for sensitizing pancreatic cancer to gemcitabine: Use of sulfasalazine (2008)
  • Xenografts of primary human gynecological tumors grown under the renal capsule of NOD/SCID mice show genetic stability during serial transplantation and respond to cytotoxic chemotherapy (2008)
    Gynecologic oncology, 110 (2), 256--264
  • 3rd PacRim Breast and Prostate Cancer Meeting: 31 October--4 November 2006, Fraser Island, Queensland, Australia (2007)
    Expert opinion on investigational drugs, 16 (3), 397--401
  • Bisphenol A induces permanent squamous change in mouse prostatic epithelium (2007)
    Differentiation, 75 (8), 745--756
  • Modulation by decitabine of gene expression and growth of osteosarcoma U2OS cells in vitro and in xenografts: identification of apoptotic genes as targets for demethylation (2007)
    Cancer cell international, 7 (1), 14
  • Molecular pathogenesis of lung cancer with translation to the clinic: M10-01 (2007)
    Journal of Thoracic Oncology, 2 (8), S178--S179
  • SAGE analysis of human metastatic and non-metastatic prostate cancer xenograft sublines from a single patient. (2007)
  • Steroid hormones and carcinogenesis of the prostate: the role of estrogens (2007)
    Differentiation, 75 (9), 871--882
  • Sulfasalazine enhances growth-inhibitory activity of doxorubicin: Potential use in combination chemotherapy of advanced prostate cancer (2007)
  • Sulfasalazine-induced cystine starvation: Potential use for prostate cancer therapy (2007)
    The Prostate, 67 (2), 162--171
  • The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression (2007)
    Cancer research, 67 (3), 967--975
  • Establishment and characterization of a novel pancreatic cancer tissue xenograft model. (2006)
  • Establishment in severe combined immunodeficiency mice of subrenal capsule xenografts and transplantable tumor lines from a variety of primary human lung cancers: potential models for studying tumor progression--related changes (2006)
    Clinical Cancer Research, 12 (13), 4043--4054
  • Isolation of tumor subpopulations with different androgen requirements from a primary human prostate cancer (2006)
  • Molecular analysis and characterization of PrEC, commercially available prostate epithelial cells (2006)
    In Vitro Cellular & Developmental Biology-Animal, 42 (1), 33--39
  • Steroid hormones stimulate human prostate cancer progression and metastasis (2006)
    International journal of cancer, 118 (9), 2123--2131
  • Sulfasalazine: Potential use of an old drug for treatment of pancreatic cancer (2006)
  • An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line (2005)
    Laboratory investigation, 85 (11), 1392--1404
  • Development and characterization of efficient xenograft models for benign and malignant human prostate tissue (2005)
    The Prostate, 64 (2), 149--159
  • Establishment of subrenal capsule xenografts of primary human ovarian tumors in SCID mice: potential models (2005)
    Gynecologic oncology, 96 (1), 48--55
  • Growth arrest by sulfasalazine (SASP) of subrenal capsule prostate cancer xenografts in immuno-deficient mice is coupled to a decrease in the number of tumor-associated macrophages (2005)
  • Histopathologic and molecular cytogenetic characterization of tumor xenografts and transplantable tumor lines from a variety of human lung cancers (2005)
    LABORATORY INVESTIGATION, 85, 309A--309A
  • Hormonal and stromal regulation of normal and neoplastic prostatic growth (2005)
    Developmental Biology of Neoplastic Growth, , 183--216
  • P-682 Development of transplantable tumor lines from a variety ofhuman lung cancers via sub-renal capsule grafting (2005)
    Lung Cancer, 49, S297--S298
  • The ontogeny of the urogenital system of the spotted hyena (Crocuta crocuta Erxleben) (2005)
    Biology of reproduction, 73 (3), 554--564
  • Hormonal, cellular, and molecular regulation of normal and neoplastic prostatic development (2004)
    The Journal of steroid biochemistry and molecular biology, 92 (4), 221--236
  • Potential use for sulfasalazine in lung cancer therapy (2004)
  • Establishing efficient xenograft models of models of low-grade human prostate cancer (2003)
    European Urology Supplements, 2 (6), 30
  • hZimp10 is an androgen receptor co-activator and forms a complex with SUMO-1 at replication foci (2003)
    The EMBO journal, 22 (22), 6101--6114
  • Quantitation of apoptotic activity following castration in human prostatic tissue in vivo (2003)
    The Prostate, 54 (3), 212--219
  • Rescue and isolation of Rb-deficient prostate epithelium by tissue recombination (2003)
    Cancer Cell Signaling: Methods and Protocols, , 17--33
  • Role of the stromal microenvironment in carcinogenesis of the prostate (2003)
    International journal of cancer, 107 (1), 1--10
  • Sulfasalazine, inhibits growth of mantle cell lymphoma (MCL) cell cultures via cyst (e) ine starvation and delays tumour growth in a newly developed murine MCL model. (2003)
    BLOOD, 102 (11), 649A--650A
  • Urogenital system of the spotted hyena (Crocuta crocuta Erxleben): a functional histological study (2003)
    Journal of Morphology, 256 (2), 205--218
  • Variation in ovarian morphology in four species of New World moles with a peniform clitoris (2003)
    Reproduction, 126 (6), 713--719
  • Nkx3. 1 mutant mice recapitulate early stages of prostate carcinogenesis (2002)
    Cancer research, 62 (11), 2999--3004
  • PROTEIN SYNTHESIS, POST-TRANSLATION MODIFICATION, AND DEGRADATION-Rescue of Embryonic Epithelium Reveals That the Homozygous Deletion of the Retinoblastoma Gene Confers Growth Factor Independence (2002)
    Journal of Biological Chemistry, 277 (46), 44475--44484
  • Rescue of embryonic epithelium reveals that the homozygous deletion of the retinoblastoma gene confers growth factor independence and immortality but does not influence epithelial differentiation or tissue morphogenesis (2002)
    Journal of Biological Chemistry, 277 (46), 44475--44484
  • Role of stroma in carcinogenesis of the prostate (2002)
    Differentiation: REVIEW, 70 (9-10), 473--485
  • A human prostatic epithelial model of hormonal carcinogenesis (2001)
    Cancer research, 61 (16), 6064--6072
  • Cell differentiation lineage in the prostate (2001)
    Differentiation, 68 (4-5), 270--279
  • Estrogenic effects on prostatic differentiation and carcinogenesis (2001)
    Reproduction, Fertility and Development, 13 (4), 285--296
  • Evidence That Epithelial and Mesenchymal Estrogen Receptor-$α$ Mediate Effects of Estrogen on Prostatic Epithelium: Volume 229, Number 2 (2001), pages 432--442 (2001)
    Developmental Biology, 231 (1), 289
  • Evidence that epithelial and mesenchymal estrogen receptor-$α$ mediates effects of estrogen on prostatic epithelium (2001)
    Developmental biology, 229 (2), 432--442
  • Malignant transformation in a nontumorigenic human prostatic epithelial cell line (2001)
    Cancer research, 61 (22), 8135--8142
  • Paracrine regulation of apoptosis by steroid hormones in the male and female reproductive system (2001)
    Cell death and differentiation, 8 (2), 192
  • Regular Articles-Carcinogenesis-The Consequences of Chromosomal Aneuploidy on Gene Expression Profiles in a Cell Line Model for Prostate Carcinogenesis. (2001)
    Cancer Research, 61 (22), 8143--8149
  • Role of estrogen signaling in prostatic hormonal carcinogenesis (2001)
    J Urol (Suppl), 165, 132--133
  • The BMP family member Gdf7 is required for seminal vesicle growth, branching morphogenesis, and cytodifferentiation (2001)
    Developmental biology, 234 (1), 138--150
  • The consequences of chromosomal aneuploidy on gene expression profiles in a cell line model for prostate carcinogenesis (2001)
    Cancer Research, 61 (22), 8143--8149
  • Changes in serum and tissue zinc levels in sex hormone-induced prostatic carcinogenesis in the noble rat (2000)
    Tumor biology, 21 (6), 328--336
  • Growth factors and epithelial-stromal interactions in prostate cancer development (2000)
    International review of cytology, 199, 65--116
  • Sex hormone-induced carcinogenesis in Rb-deficient prostate tissue (2000)
    Cancer research, 60 (21), 6008--6017
  • Prostatic Epithelial Apoptosis Following Castration Does Not Require Epithelial Androgen Receptors (1999)
    The Journal of Urology, 161 (4S), 51
  • Sex hormone-induced prostatic carcinogenesis in the Noble rat: The role of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) in the development of prostate cancer (1998)
    The Prostate, 35 (3), 165--177
  • The prostate gland and prostate carcinogenesis. (1998)
    Italian journal of anatomy and embryology= Archivio italiano di anatomia ed embriologia, 103 (4 Sup), 237--252
  • Oncogenes and tumor suppressor genes in prostate cancer: a review (1997)
    Urologic Oncology: Seminars and Original Investigations, 3 (2), 41--46
  • The evaluation of biomarkers in sex hormone-induced prostatic carcinogenesis in the Noble (Nb) rat (1997)
    香港大學學位論文, , 1--0
  • The influence of mesenchyme of neonatal seminal vesicle and embryonic urogenital sinus on the morphologic and functional cytodifferentiation of Dunning prostatic adenocarcinoma: roles of growth factors and proto-oncogenes (1997)
    Urologic Oncology: Seminars and Original Investigations, 3 (3), 85--93
  • Differential Expression of transforming growth factor-a (TGF-a) in dorsolateral (DLP) and ventral prostate (VP) during prostate carcinogenesis (1996)
    Proceedings of the American Association for Cancer Research,
  • Association of transforming growth factor-B with cytodifferentiation of prostatic dunning tumor (1995)
    86th Annual Meeting: American Association for Cancer Research,
  • Influence of mesenchyme on the expression of c-fos and c-jun proto-oncogenes in rat prostatic dunning tumour (DT) (1995)
    Proceedings of the International Conference on Androgenic Hormones, Prostatic Cancer and Benign Prostatic Hyperplasia,
 
 

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