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The role of glutamine metabolism in castration-resistant prostate cancer

Asian Journal of Andrology 2023年第2期25卷 192-197页

作者： Bing Zhao Jing Wang Li Chen Hong Wang Chao-Zhao Liang jiaoti huang Ling-Fan Xu Department of Geriatrics The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230002China Department of Urologic Oncology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230031China Department of Nursing The First Affiliated Hospital of Anhui Medical UniversityHefei 230001China Department of Urology The First Affiliated Hospital of Anhui Medical UniversityHefei 230001China Institute of Urology Anhui Medical UniversityHefei 230001China Anhui Province Key Laboratory of Genitourinary Diseases Anhui Medical UniversityHefei 230001China Department of Pathology Duke University School of MedicineDurhamNC 27710USA Duke Cancer Institute Duke University School of MedicineDurhamNC 27710USA

Reprogramming of metabolism is a hallmark of tumors,which has been explored for therapeutic *** cancer(PCa),particularly advanced and therapy-resistant PCa,displays unique metabolic *** metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical *** the many nutrients,glutamine has been shown to play a central role in the metabolic reprogramming of advanced *** addition to amino acid metabolism,glutamine is also widely involved in the synthesis of other macromolecules and *** glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many *** review summarizes the metabolic landscape of PCa,with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa,and suggests novel therapeutic strategies.

关键词： castration resistance glutamine metabolism prostate cancer tumor metabolism

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Prostate cancer: molecular and cellular mechanisms and their implications in therapy resistance and disease progression

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Asian Journal of Andrology 2019年第3期21卷 213-214页

作者： Ninghan Feng jiaoti huang Department of Urology Affiliated Wuxi No. 2 Hospital Nanjing Medical University Wuxi 214002 China Department of Pathology Duke University School of Medicine Durham NC 27514 USA

Prostate cancer is among the most common malignancies in Western countries, and its incidence is rapidly rising in Asia where it was traditionally considered an uncommon tumor. Our understanding of the disease and management strategies continue to evolve. The first revolution of its treatment was in the 1940s when hormonal therapy was used to treat patients.

关键词： Prostate cancer is among malignancies in Western treat patients

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Targeted prostate biopsy： value of multiparametric magnetic resonance imaging in detection of localized cancer

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Asian Journal of Andrology 2014年第4期16卷 522-529页

作者： Jesse D Le jiaoti huang Leonard S Marks Departments of Urology University of California Los Angeles USA. Pathology University of California Los Angeles USA.

Prostate cancer is the second most common cancer in men, with 1.1 million new cases worldwide reported by the World Health Organization in one recent year. Transrectal ultrasound （TRUS）-guided biopsy has been used for the diagnosis of prostate cancer for over 2 decades, but the technique is usually blind to cancer location. Moreover, the false negative rate of TRUS biopsy has been reported to be as high as 47%. Multiparametric magnetic resonance imaging （mp-MRI） includes T1- and T2-weighted imaging as well as dynamic contrast-enhanced （DCE） and diffusion-weighted imaging （DWI）. mp-MRI is a major advance in the imaging of prostate cancer, enabling targeted biopsy of suspicious lesions. Evolving targeted biopsy techniquesmincluding direct in-bore biopsy, cognitive fusion and software-based MRI-ultrasound （MRI-US） fusion--have led to a several-fold improvement in cancer detection compared to the earlier method. Importantly, the detection of clinically significant cancers has been greatly facilitated by targeting, compared to systematic biopsy alone. Targeted biopsy via MRI-US fusion may dramatically alter the way prostate cancer is diagnosed and managed.

关键词： fusion biopsy magnetic resonance imaging (MRI) prostate biopsy prostate cancer targeted biopsy ultrasound

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Neuroendocrine cells of the prostate:Histology,biological functions,and molecular mechanisms

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Precision Clinical Medicine 2021年第1期4卷 25-34页

作者： William Butler jiaoti huang Department of Pathology Duke University School of MedicineDurhamNC 27710USA

Prostate cancer(PCa)is a common cause of cancer-related mortality inmen *** most men are diagnosed with low grade,indolent tumors that are potentially curable,a significant subset develops advanced disease where hormone therapy is required to target the androgen receptor(AR).Despite its initial effect,hormone therapy eventually fails and the tumor progresses to lethal stages even through continued inhibition of *** review article focuses on the role of PCa cellular heterogeneity in therapy resistance and disease *** AR-positive luminal-type cells represent the vast majority of PCa cells,there exists a minor component of AR-negative neuroendocrine(NE)cells that are resistant to hormonal therapy and are enriched by the *** addition,it is now well accepted that a significant subset of hormonally treated tumors recur as small cell neuroendocrine carcinoma(SCNC),further highlighting the importance of targeting NE cells in addition to the more abundant luminal-type cancer *** it has been long recognized that NE cells are present in PCa,their underlying function in benign prostate and molecular mechanisms contributing to PCa progression remains poorly *** this article,we review the morphology and function of NE cells in benign prostate and PCa as well as underlying molecular *** addition,we review the major reported mechanisms for transformation from common adenocarcinoma histology to the highly lethal SCNC,a significant clinical challenge in the management of advanced PCa.

关键词： prostate cancer neuroendocrine

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The molecular basis for ethnic variation and histological subtype differences in prostate cancer

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Science China(Life Sciences) 2013年第9期56卷 780-787页

作者： ZONG Yang GOLDSTEIN Andrew S. huang jiaoti Howard Hughes Medical Institute University of California Departments of Molecular and Medical Pharmacology University of California Urology University of California Jonsson Comprehensive Cancer Center David Geffen School of Medicine University of California Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research University of California Pathology and Laboratory Medicine University of California

Prostate cancer is a common malignancy among men in Western countries. Recently the morbidity and mortality of prostate cancer increase dramatically in several oriental countries including China. Rapidly evolving technology in molecular biology such as high-throughput sequencing and integrative analysis of genomic and transcriptomic landscapes have enabled the identification of key oncogenic events for prostate cancer initiation, progression and resistance to hormonal therapy. These surging data of prostate cancer genome also provide insights on ethnic variation and the differences in histological subtype of this disease. In this review, differences in the incidence of prostate cancer and the prevalence of main genetic alterations between Asian and Western populations are discussed. We also review the recent findings on the mechanisms underlying neuroendocrine differentiation of prostate cancer and the development of small cell neuroendocrine carcinoma after androgen deprivation therapy.

关键词：前列腺癌种族差异组织学分子基础亚型神经内分泌西方国家基因组学

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The expanded role of fatty acid metabolism in cancer:new aspects and targets

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Precision Clinical Medicine 2019年第3期2卷 183-191页

作者： Ming Chen jiaoti huang Department of Pathology Duke University School of MedicineDuke Cancer InstituteDuke UniversityDurhamNC 27514USA

Cancer cells undergo metabolic reprogramming to support cell proliferation,growth,and *** in lipid metabolism,and specifically the uptake and synthesis of fatty acids(FAs),comprise onewelldocumented aspect of this *** studies have revealed an expanded range of roles played by FA in promoting the aggressiveness of cancer while simultaneously identifying new potential targets for cancer *** article provides a brief review of these advances in our understanding of FA metabolism in cancer,highlighting both recent discoveries and the inherent challenges caused by the metabolic plasticity of cancer cells in targeting lipid metabolism for cancer therapy.

关键词： cancer fatty acid metabolism lipid metabolism metabolic plasticity

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Novel genetic loci associated with prostate cancer in the rapanese population

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Asian Journal of Andrology 2011年第1期13卷 120-121页

作者： Yin Sun jiaoti huang Department of Pathology and Laboratory Medicine Jonsson Comprehensive Cancer Center and Broad Center for Regenerative Medicine and Stem Cell Biology University of California at Los Angeles Los Angeles CA 90095 USA

Takata et al.1 recently reported in Nature Genetics that they have identified five novel genetic loci that are associated with prostate cancer in the Japanese population. Using most updated Illumina Quad BeadChip to g...

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Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2329-2344页

作者： Junhui Hu Ping Tan Moe Ishihara Nicholas ABayley Shiruyeh Schokrpur Jeremy GReynoso Yangjun Zhang Raymond JLim Camelia Dumitras Lu Yang Steven MDubinett Parmjit SJat Jacques Van Snick jiaoti huang Arnold IChin Robert MPrins Thomas GGraeber Hua Xu Lily Wu Department of Molecular and Medical Pharmacology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Department of Urology West China HospitalChengduChina Department of Hematology and Oncology University of California San DiegoSan DiegoCA92103USA Department of Neurosurgery David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Department of Biological Repositories Department of UrologyZhongnan Hospital of Wuhan UniversityWuhanChina Department of Medicine David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Jonsson Comprehensive Cancer Center David Geffen School of Medicine at UCLAUniversity of California Los AngelesLos AngelesCA90095USA MRC Prion Unit at UCL Institute of Prion Diseases33 Cleveland StreetLondonW1W 7FFUK Ludwig Institute for Cancer Research Ltd BrusselsBelgium Department of Pathology Duke UniversityDurhamNCUSA Department of Urology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center WuhanChina

Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under *** study the impact of intratumoral VHL heterogeneity observed in human ccRCC,we engineered VHL gene deletion in four RCC models,including a new primary tumor cell line derived from an aggressive metastatic *** VHL gene-deleted(VHL-KO)cells underwent epithelial-to-mesenchymal transition(EMT)and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing(VHL+)*** tumors with either VHL+or VHL-KO cells alone exhibit minimal metastatic *** tumors displayed rampant lung metastases,highlighting a novel cooperative metastatic *** poorly proliferative VHL-KO cells stimulated the proliferation,EMT,and motility of neighboring VHL+***(POSTN),a soluble protein overexpressed and secreted by VHL non-expressing(VHL−)cells,promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular *** deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical *** work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.

关键词： VHL metastasis motility

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Targeting androgen receptor-independent pathways in therapy-resistant prostate cancer

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Asian Journal of Urology 2019年第1期6卷 91-98页

作者： Lingfan Xu Junyi Chen Weipeng Liu Chaozhao Liang Hailiang Hu jiaoti huang Department of Urology The First Affiliated Hospital of Anhui Medical UniversityHefeiChina Department of Pathology Duke University School of MedicineDurhamNCUSA Department of Urology The Second Affiliated Hospital of Fujian Medical UniversityQuanzhouChina Department of Urology The First Affiliated Hospital of Nanchang UniversityNanchangChina

Since androgen receptor(AR)signaling is critically required for the development of prostate cancer(PCa),targeting AR axis has been the standard treatment of choice for advanced and metastatic ***,although the tumor initially responds to the therapy,treatment resistance eventually develops and the disease will *** is therefore imperative to identify the mechanisms of therapeutic resistance and novel molecular targets that are independent of AR *** advances in pathology,molecular biology,genetics and genomics research have revealed novel AR-independent pathways that contribute to PCa carcinogenesis and *** include neuroendocrine differentiation,cell metabolism,DNA damage repair pathways and immune-mediated *** development of novel agents targeting the non-AR mechanisms holds great promise to treat PCa that does not respond to AR-targeted therapies.

关键词： Prostate cancer Therapeutic resistance Androgen receptor Neuroendocrine Cancer metabolism DNA damage repair

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The promise of immunotherapy in genitourinary malignancies

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Precision Clinical Medicine 2018年第3期1卷 97-101页

作者： Tian Zhang Andrew J.Armstrong Daniel J.George jiaoti huang Duke Cancer Institute Duke University School of MedicineDurhamNC27514

A broad understanding of the tumor immune landscape has led to a revolution of immune checkpoint inhibitors in the treatment of multiple cancer *** genitourinary malignancies,immune checkpoint inhibitors have improved outcomes for patients with metastatic renal cell carcinoma and metastatic urothelial carcinoma;however,these treatments have not yet proven broadly beneficial for patients with metastatic prostate *** prospective trials are ongoing to further improve outcomes with immunotherapy combinations and for biomarker development to predict benefit from immune checkpoint *** perspective article highlights our current immunotherapy approaches in each of the genitourinary malignancies and the ongoing clinical trials that may inform our future treatments in renal,urothelial,and prostate cancers.

关键词： immune checkpoint inhibition urothelial carcinoma renal cell carcinoma prostate cancer

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