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Androgen Receptor Signaling in Castration-Resistant Prostate Cancer Alters Hyperpolarized Pyruvate to Lactate Conversion and Lactate Levels In Vivo.
Zacharias, Niki; Lee, Jaehyuk; Ramachandran, Sumankalai; Shanmugavelandy, Sriram; McHenry, James; Dutta, Prasanta; Millward, Steven; Gammon, Seth; Efstathiou, Eleni; Troncoso, Patricia; Frigo, Daniel E; Piwnica-Worms, David; Logothetis, Christopher J; Maity, Sankar N; Titus, Mark A; Bhattacharya, Pratip.
Afiliação
  • Zacharias N; Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1907, Houston, TX, 77054, USA.
  • Lee J; Department of Bioengineering, Rice University, Houston, TX, USA.
  • Ramachandran S; Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Shanmugavelandy S; Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1907, Houston, TX, 77054, USA.
  • McHenry J; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Dutta P; Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1907, Houston, TX, 77054, USA.
  • Millward S; Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1907, Houston, TX, 77054, USA.
  • Gammon S; Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1907, Houston, TX, 77054, USA.
  • Efstathiou E; Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1907, Houston, TX, 77054, USA.
  • Troncoso P; Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1907, Houston, TX, 77054, USA.
  • Frigo DE; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Piwnica-Worms D; Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
  • Logothetis CJ; Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1907, Houston, TX, 77054, USA.
  • Maity SN; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Titus MA; Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1907, Houston, TX, 77054, USA.
  • Bhattacharya P; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mol Imaging Biol ; 21(1): 86-94, 2019 02.
Article em En | MEDLINE | ID: mdl-29748904
PURPOSE: Androgen receptor (AR) signaling affects prostate cancer (PCa) growth, metabolism, and progression. Often, PCa progresses from androgen-sensitive to castration-resistant prostate cancer (CRPC) following androgen-deprivation therapy. Clinicopathologic and genomic characterizations of CRPC tumors lead to subdividing CRPC into two subtypes: (1) AR-dependent CRPC containing dysregulation of AR signaling alterations in AR such as amplification, point mutations, and/or generation of splice variants in the AR gene; and (2) an aggressive variant PCa (AVPC) subtype that is phenotypically similar to small cell prostate cancer and is defined by chemotherapy sensitivity, gain of neuroendocrine or pro-neural marker expression, loss of AR expression, and combined alterations of PTEN, TP53, and RB1 tumor suppressors. Previously, we reported patient-derived xenograft (PDX) animal models that contain characteristics of these CRPC subtypes. In this study, we have employed the PDX models to test metabolic alterations in the CRPC subtypes. PROCEDURES: Mass spectrometry and nuclear magnetic resonance analysis along with in vivo hyperpolarized 1-[13C]pyruvate spectroscopy experiments were performed on prostate PDX animal models. RESULTS: Using hyperpolarized 1-[13C]pyruvate conversion to 1-[13C]lactate in vivo as well as lactate measurements ex vivo, we have found increased lactate production in AR-dependent CRPC PDX models even under low-hormone levels (castrated mouse) compared to AR-negative AVPC PDX models. CONCLUSIONS: Our analysis underscores the potential of hyperpolarized metabolic imaging in determining the underlying biology and in vivo phenotyping of CRPC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Imageamento por Ressonância Magnética / Espectroscopia de Ressonância Magnética / Receptores Androgênicos / Ácido Láctico / Ácido Pirúvico / Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Mol Imaging Biol Assunto da revista: BIOLOGIA MOLECULAR / DIAGNOSTICO POR IMAGEM Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Imageamento por Ressonância Magnética / Espectroscopia de Ressonância Magnética / Receptores Androgênicos / Ácido Láctico / Ácido Pirúvico / Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Mol Imaging Biol Assunto da revista: BIOLOGIA MOLECULAR / DIAGNOSTICO POR IMAGEM Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos