9,611 results match your criteria androgen signaling


Targeting KDM4B that coactivates c-Myc-regulated metabolism to suppress tumor growth in castration-resistant prostate cancer.

Theranostics 2021 26;11(16):7779-7796. Epub 2021 Jun 26.

Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing-Hua University, Hsinchu 30013, Taiwan.

The progression of prostate cancer (PCa) to castration-resistant PCa (CRPC) despite continuous androgen deprivation therapy is a major clinical challenge. Over 90% of patients with CRPC exhibit sustained androgen receptor (AR) signaling. KDM4B that removes the repressive mark H3K9me3/2 is a transcriptional activator of AR and has been implicated in the development of CRPC. Read More

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Classic and Novel Sex Hormone Binding Globulin Effects on the Cardiovascular System in Men.

Int J Endocrinol 2021 21;2021:5527973. Epub 2021 Jul 21.

Programa de Fisiología y Biofísica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8389100, Chile.

In men, 70% of circulating testosterone binds with high affinity to plasma sex hormone binding globulin (SHBG), which determines its bioavailability in their target cells. In recent years, a growing body of evidence has shown that circulating SHBG not only is a passive carrier for steroid hormones but also actively regulates testosterone signaling through putative plasma membrane receptors and by local expression of androgen-binding proteins apparently to reach local elevated testosterone concentrations in specific androgen target tissues. Circulating SHBG levels are influenced by metabolic and hormonal factors, and they are reduced in obesity and insulin resistance, suggesting that SHBG may have a broader clinical utility in assessing the risk for cardiovascular diseases. Read More

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Lutetium PSMA-617 and idronoxil (NOX66) in men with end-stage metastatic castrate-resistant prostate cancer (LuPIN): Patient outcomes and predictors of treatment response of a Phase I/II trial.

J Nucl Med 2021 Jul 29. Epub 2021 Jul 29.

Department of Theranostics and Nuclear Medicine, St Vincent's Hospital, Australia.

Lutetium PSMA-617 (Lu-PSMA-617) is an effective therapy for metastatic castrate-resistant prostate cancer (mCRPC). However, treatment resistance occurs frequently and combination therapies may improve outcomes. We report the final safety and efficacy results of a phase I/II study combining Lu-PSMA-617 with idronoxil (NOX66), a radiosensitiser, and examined potential clinical, blood-based and imaging biomarkers. Read More

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Histone acetyltransferase 1 upregulates androgen receptor expression to modulate CRPC cell resistance to enzalutamide.

Clin Transl Med 2021 Jul;11(7):e495

Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.

Castration-resistant prostate cancer (CRPC) is the latest stage of PCa, and there is almost no effective treatment available for the patients with CRPC when next-generation androgen deprivation therapy drugs, such as enzalutamide (ENZ), fail. The androgen receptor (AR) plays key roles in PCa and CRPC progression and drug resistance. Histone acetyltransferase 1 (HAT1) has recently been reported to be highly expressed in some tumors, such as lung carcinoma. Read More

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Loss of in Prostate Cancer Correlates With Clinical Response to Androgen Deprivation Therapy.

JCO Precis Oncol 2021 Jun 22;5. Epub 2021 Jun 22.

Department of Surgery, University of Melbourne, Parkville, Victoria, Australia.

Purpose: Androgen receptor (AR) signaling is important in prostate cancer progression, and therapies that target this pathway have been the mainstay of treatment for advanced disease for over 70 years. Tumors eventually progress despite castration through a number of well-characterized mechanisms; however, little is known about what determines the magnitude of response to short-term pathway inhibition.

Methods: We evaluated a novel combination of AR-targeting therapies (degarelix, abiraterone, and bicalutamide) and noted that the objective patient response to therapy was highly variable. Read More

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CRISPR screening identifies CDK12 as a conservative vulnerability of prostate cancer.

Cell Death Dis 2021 Jul 27;12(8):740. Epub 2021 Jul 27.

Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.

Androgen receptor (AR) signaling inhibitors provide limited survival benefits to patients with prostate cancer (PCa), and worse, few feasible genomic lesions restrict targeted treatment to PCa. Thus, a better understanding of the critical dependencies of PCa may enable more feasible therapeutic approaches to the dilemma. We performed a kinome-scale CRISPR/Cas9 screen and identified cyclin-dependent kinase 12 (CDK12) as being conservatively required for PCa cell survival. Read More

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Insulin signaling, androgen receptor and PSMA immunohistochemical analysis by semi-automated tissue microarray in prostate cancer with diabetes (DIAMOND study).

Transl Res 2021 Jul 24. Epub 2021 Jul 24.

Urology Section, Department of Surgery, University of Catania, Catania, Italy. Electronic address:

In the last years, many studies have highlighted the hypothesis that diabetes and hyperglycemia could be relevant for prostate cancer (PC) development and progression. We aimed to identify the prognostic value of tissue expression of androgen receptor (AR), Prostate-Specific Membrane Antigen (PSMA), Ki-67, insulin receptors (IR)  α and β, insulin growth factor-1 (IGF-1) receptor, in patients with PC and to evaluate their association with diabetes. We retrospectively collected data from 360 patients who underwent radical prostatectomy for PC or surgery for benign prostatic hyperplasia (BPH), between 2010 and 2020. Read More

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Emerging impact of quercetin in the treatment of prostate cancer.

Biomed Pharmacother 2021 Jun 1;138:111548. Epub 2021 Apr 1.

Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Quercetin is a flavonoid agent detected in fruits and vegetables with anti-inflammatory, antioxidant, and anticancer effects. This flavonoid can suppress cell cycle transition and induce apoptosis in neoplastic cells. Therapeutic effects of quercetin have been assessed in diverse cancers including prostate cancer through the establishment of in vitro and in vivo experiments. Read More

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Macrophage-derived cholesterol contributes to therapeutic resistance in prostate cancer.

Cancer Res 2021 Jul 23. Epub 2021 Jul 23.

Immunology, Moffitt Cancer Center

Castration-resistant prostate cancer (CRPC) is a lethal stage of disease in which androgen receptor (AR) signaling is persistent despite androgen deprivation therapy (ADT). Most studies have focused on investigating cell-autonomous alterations in CRPC, while the contributions of the tumor microenvironment are less well understood. Here we sought to determine the role of tumor-associated macrophages in CRPC, based upon their role in cancer progression and therapeutic resistance. Read More

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Androgen/Androgen Receptor Signaling in Ovarian Cancer: Molecular Regulation and Therapeutic Potentials.

Int J Mol Sci 2021 Jul 20;22(14). Epub 2021 Jul 20.

Sex Hormone Research Center, Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung 40403, Taiwan.

Ovarian cancer (OVCA) arises from three cellular origins, namely surface epithelial cells, germ cells, and stromal cells. More than 85% of OVCAs are EOCs (epithelial ovarian carcinomas), which are the most lethal gynecological malignancies. Cancer stem/progenitor cells (CSPCs) are considered to be cancer promoters due to their capacity for unlimited self-renewal and drug resistance. Read More

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Predictive and Prognostic Biomarker Identification in a Large Cohort of Androgen Receptor-Positive Salivary Duct Carcinoma Patients Scheduled for Combined Androgen Blockade.

Cancers (Basel) 2021 Jul 14;13(14). Epub 2021 Jul 14.

Department of Urology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.

Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). However, CAB frequently fails, resulting in a worse prognosis. Therefore, biomarkers that can predict treatment failure are urgently needed. Read More

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Differential but Concerted Expression of HSD17B2, HSD17B3, SHBG and SRD5A1 Testosterone Tetrad Modulate Therapy Response and Susceptibility to Disease Relapse in Patients with Prostate Cancer.

Cancers (Basel) 2021 Jul 12;13(14). Epub 2021 Jul 12.

Department of Urology, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan.

: Testosterone plays a critical role in prostate development and pathology. However, the impact of the molecular interplay between testosterone-associated genes on therapy response and susceptibility to disease relapse in PCa patients remains underexplored. : This study investigated the role of dysregulated or aberrantly expressed testosterone-associated genes in the enhanced dissemination, phenoconversion, and therapy response of treatment-resistant advanced or recurrent PCa. Read More

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Interplay of Epidermal Growth Factor Receptor and Signal Transducer and Activator of Transcription 3 in Prostate Cancer: Beyond Androgen Receptor Transactivation.

Cancers (Basel) 2021 Jul 9;13(14). Epub 2021 Jul 9.

Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.

Prostate cancer (PCa) is one of the most common cancers in the world and causes thousands of deaths every year. Conventional therapy for PCa includes surgery and androgen deprivation therapy (ADT). However, about 10-20% of all PCa cases relapse; there is also the further development of castration resistant adenocarcinoma (CRPC-Adeno) or neuroendocrine (NE) PCa (CRPC-NE). Read More

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Characterization of Novel Progression Factors in Castration-Resistant Prostate Cancer Based on Global Comparative Proteome Analysis.

Cancers (Basel) 2021 Jul 8;13(14). Epub 2021 Jul 8.

BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy, Kyungpook National University, Daegu 41566, Korea.

Identifying the biological change from hormone-naïve prostate cancer to castration-resistant prostate cancer (CRPC) is a major clinical challenge for developing therapeutic agents. Although the pathways that lead to CRPC are not fully completely understood, recent evidence demonstrates that androgen signaling is often maintained through varied mechanisms. Androgen deprivation therapy (ADT) is used as a primary treatment for preventing the progression of prostate cancer (PCa). Read More

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Suppressive Effect and Molecular Mechanism of Thunb. Extract against Prostate Carcinogenesis and Castration-Resistant Prostate Cancer.

Cancers (Basel) 2021 Jul 7;13(14). Epub 2021 Jul 7.

Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.

Thunb. (HCT) is a well-known Asian medicinal plant with biological activities used in the treatment of many diseases including cancer. This study investigated the effects of HCT extract and its ethyl acetate fraction (EA) on prostate carcinogenesis and castration-resistant prostate cancer (CRPC). Read More

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SHH-N non-canonically sustains androgen receptor activity in androgen-independent prostate cancer cells.

Sci Rep 2021 Jul 21;11(1):14880. Epub 2021 Jul 21.

Laboratory for Hereditary Cancer, Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička 54, 10000, Zagreb, Croatia.

Prostate cancer is the second most frequent cancer diagnosed in men worldwide. Localized disease can be successfully treated, but advanced cases are more problematic. After initial effectiveness of androgen deprivation therapy, resistance quickly occurs. Read More

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A Phase 1 study Combining Pexidartinib, Radiation Therapy, and Androgen Deprivation Therapy in Men With Intermediate- and High-Risk Prostate Cancer.

Adv Radiat Oncol 2021 Jul-Aug;6(4):100679. Epub 2021 Mar 3.

Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.

Purpose: This study aimed to evaluate a combination of radiation therapy (RT), androgen deprivation therapy (ADT), and pexidartinib (colony-stimulating factor 1 receptor [CSF1R]) inhibitor in men with intermediate- and high-risk prostate cancer. CSF1R signaling promotes tumor infiltration and survival of tumor-associated macrophages, which in turn promote progression and resistance. Counteracting protumorigenic actions of tumor-associated macrophages via CSF1R inhibition may enhance therapeutic efficacy of RT and ADT for prostate cancer. Read More

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Chromatin and Epigenetic Dysregulation of Prostate Cancer Development, Progression, and Therapeutic Response.

Cancers (Basel) 2021 Jul 2;13(13). Epub 2021 Jul 2.

Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0424 Oslo, Norway.

The dysregulation of chromatin and epigenetics has been defined as the overarching cancer hallmark. By disrupting transcriptional regulation in normal cells and mediating tumor progression by promoting cancer cell plasticity, this process has the ability to mediate all defined hallmarks of cancer. In this review, we collect and assess evidence on the contribution of chromatin and epigenetic dysregulation in prostate cancer. Read More

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Androgen receptor antagonists produced by Streptomyces overcome resistance to enzalutamide.

J Antibiot (Tokyo) 2021 Jul 19. Epub 2021 Jul 19.

Showa Pharmaceutical University, Machida, Tokyo, Japan.

Prostate cancer (PC) is a leading cause of cancer-related death in men in Western countries. Androgen receptor (AR) signaling is a major driver of PC; therefore, androgen deprivation by medical and surgical castration is the standard treatment for patients with PC. However, over time, most patients will progress to metastatic castration-resistant PC. Read More

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A Phase I, Open-Label, Dose-Finding Study of GSK2636771, a PI3Kβ inhibitor, Administered with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer.

Clin Cancer Res 2021 Jul 19. Epub 2021 Jul 19.

Clinical Studies, Institute of Cancer Research

Purpose: In patients with metastatic castration-resistant prostate cancer (mCRPC), resistance to androgen receptor (AR) targeted therapies, such as enzalutamide, remains an issue. Inactivation of inhibitory phosphatase and tensin homolog (PTEN) activates phosphoinositide 3-kinase (PI3K)/AKT signaling and contributes to resistance to androgen-deprivation therapy and poor outcomes. Therefore, dual targeting of AR and PI3K/AKT pathways may limit tumor growth and reverse resistance. Read More

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Androgens enhance the ability of intratumoral macrophages to promote breast cancer progression.

Oncol Rep 2021 Sep 19;46(3). Epub 2021 Jul 19.

Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Miyagi‑ken 980‑8575, Japan.

Androgens are produced locally in breast carcinoma tissues by androgen‑producing enzymes such as 5α‑reductase type 1 (5αRed1) and affect not only breast cancer cells but the tumor microenvironment as well. Tumor‑associated macrophages (TAMs) are primary components of the tumor microenvironment and contribute to tumor progression. Although previous studies suggest that androgen/androgen receptor (AR) signaling in macrophages has important roles in human diseases, androgen action on TAMs has remained largely unknown. Read More

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September 2021

Enzalutamide-Induced Upregulation of PCAT6 Promotes Prostate Cancer Neuroendocrine Differentiation by Regulating miR-326/HNRNPA2B1 Axis.

Front Oncol 2021 30;11:650054. Epub 2021 Jun 30.

Department of Urology, Tongji Hospital, Tongji University of Medicine, Shanghai, China.

Our previous studies have demonstrated that Enzalutamide-induced upregulation of long non-coding RNA p21 (lncRNA-p21) facilitates prostate cancer (PCa) neuroendocrine differentiation (NED). Given the important role of lncRNAs in PCa pathogenesis, and given that lots of lncRNAs are dys-regulated in neuroendocrine PCa (NEPC) patients, we next explored the biological function and underlying mechanism of lncRNA-PCAT6 (PCAT6) in mediating Enzalutamide-induced NED. The level of PCAT6 in Enzalutamide-treated PCa cells and NEPC samples were assessed using quantitative RT-PCR (qPCR). Read More

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Sildenafil augments fetal weight and placental adiponectin in gestational testosterone-induced glucose intolerant rats.

Toxicol Rep 2021 30;8:1358-1368. Epub 2021 Jun 30.

HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.

Testosterone induces intra-uterine growth restriction (IUGR) with maternal glucose dysregulation and oxidant release in various tissues. Adiponectin, which modulates the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is expressed in the placenta and affects fetal growth. Sildenafil, a phosphodiesterase type 5 inhibitor (PDE5i), used mainly in erectile dysfunction has been widely studied as a plausible pharmacologic candidate in IUGR. Read More

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ARVib suppresses growth of advanced prostate cancer via inhibition of androgen receptor signaling.

Oncogene 2021 Jul 16. Epub 2021 Jul 16.

Department of Urologic Surgery, University of California Davis, Davis, CA, USA.

Targeting androgen signaling with the second-generation anti-androgen drugs, such as enzalutamide (Enza), abiraterone (Abi), apalutamide (Apal), and darolutamide (Daro), is the mainstay for the treatment of castration-resistant prostate cancer (CRPC). While these treatments are effective initially, resistance occurs frequently. Continued expression of androgen receptor (AR) and its variants such as AR-V7 despite AR-targeted therapy contributes to treatment resistance and cancer progression in advanced CRPC patients. Read More

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Lower androgen levels promote abnormal cartilage development in female patients with adolescent idiopathic scoliosis.

Ann Transl Med 2021 May;9(9):784

Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.

Background: Adolescent idiopathic scoliosis (AIS) is a disease characterized by changes in the three-dimensional structure of the spine. Studies have shown that the development of AIS might be associated with genetic, biomechanics, endocrine factors and abnormal bone or cartilage development.

Methods: Blood samples collected from 301 female patients (161 females with AIS and 140 females without AIS) were used for genotyping. Read More

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PARP7 mono-ADP-ribosylates the Agonist Conformation of the Androgen Receptor in the Nucleus.

Biochem J 2021 Jul 15. Epub 2021 Jul 15.

University of Virginia, Charlottesville, Virginia, United States.

We recently described a signal transduction pathway that contributes to androgen receptor (AR) regulation based on site-specific ADP-ribosylation by PARP7, a mono-ADP-ribosyltransferase implicated in several human cancers. ADP-ribosylated AR is recognized by PARP9/DTX3L, a heterodimeric complex that contains an ADP-ribose reader (PARP9) and a ubiquitin E3 ligase (DTX3L).  Here, we have characterized the cellular and biochemical requirements for AR ADP-ribosylation by PARP7. Read More

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Transcriptomic landscape of male and female reproductive cancers: Similar pathways and molecular signatures predicting response to endocrine therapy.

Mol Cell Endocrinol 2021 Jul 8;535:111393. Epub 2021 Jul 8.

Department of Structural and Functional Biology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, 18618-689, São Paulo, Brazil. Electronic address:

Reproductive cancers in both genders represent serious health problems, whose incidence has significantly risen over the past decades. Although considerable differences among reproductive cancers exist, we aimed to identify similar signaling pathways and key molecular oncomarkers shared among six human reproductive cancers that can advance the current knowledge of cancer biology to propose new strategies for more effective therapies. Using a computational analysis approach, here we uncover aberrant miRNAs-mRNAs networks shared in six reproductive tumor types, and identify common molecular mechanisms strictly associated with cancer promotion and aggressiveness. Read More

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MIF-mediated NF-κB signaling pathway regulates the pathogenesis of polycystic ovary syndrome in rats.

Cytokine 2021 Jul 6;146:155632. Epub 2021 Jul 6.

Department of Reproduction and Genetics, Reproductive Medical Centre, The First People(,)s Hospital of Yunnan Province, 650000, China. Electronic address:

Polycystic ovary syndrome (PCOS) resulting from abnormal glucose metabolism is a relatively common and complex endocrine disorder among women in their reproductive years, However, the pathogenesis of PCOS is still unclear. The purpose of this study is to investigate the macrophage migration inhibitory factor (MIF) involvement of the nuclear factor (NF)-κB in rats with PCOS. Results indicated that testosterone promoted the increase in the levels of MIF and luteinizing hormone (LH) but inhibited the increase in the level of follicular stimulating hormone (FSH). Read More

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Clascoterone: a new topical anti-androgen for acne management.

Int J Dermatol 2021 Jul 9. Epub 2021 Jul 9.

Department of Dermatology, Malabar Medical College Hospital and Research Centre, Kozhikode, India.

Clascoterone is an androgen receptor inhibitor which has been approved by the United States Food and Drug Administration for the topical treatment of acne vulgaris in patients 12 years of age and older. It competes with androgens, especially dihydrotestosterone, for androgen-receptor binding and limits their binding, thus inhibiting downstream signaling of pathways involved in the pathogenesis of acne. It inhibits androgen receptor-regulated gene transcription, and antagonizes lipid and inflammatory cytokine production in a dose-dependent manner in human primary sebocytes. Read More

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Sex-dependent dynamics of metabolism in primary mouse hepatocytes.

Arch Toxicol 2021 Jul 9. Epub 2021 Jul 9.

Faculty of Medicine, Rudolf-Schönheimer-Institute of Biochemistry, Leipzig University, Leipzig, Germany.

The liver is one of the most sexually dimorphic organs. The hepatic metabolic pathways that are subject to sexual dimorphism include xenobiotic, amino acid and lipid metabolism. Non-alcoholic fatty liver disease and hepatocellular carcinoma are among diseases with sex-dependent prevalence, progression and outcome. Read More

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