Isotope Tracing of Human Clear Cell Renal Cell Carcinomas Demonstrates Suppressed Glucose Oxidation In Vivo

Courtney Kevin D.; Bezwada Divya; Mashimo Tomoyuki; Pichumani Kumar; Vemireddy Vamsidhara; Funk Alexander M.; Wimberly Jennifer; McNeil Sarah S.; Kapur Payal; Lotan Yair; Margulis Vitaly; Cadeddu Jeffrey A.; Pedrosa Ivan; DeBerardinis Ralph J.; Malloy Craig R.; Bachoo Robert M.; Maher Elizabeth A.

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Isotope Tracing of Human Clear Cell Renal Cell Carcinomas Demonstrates Suppressed Glucose Oxidation In Vivo

机译：人透明细胞肾细胞癌的同位素描绘证明体内抑制葡萄糖氧化

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Clear cell renal cell carcinoma (ccRCC) is the most common form of human kidney cancer. Histological and molecular analyses suggest that ccRCCs have significantly altered metabolism. Recent human studies of lung cancer and intracranial malignancies demonstrated an unexpected preservation of carbohydrate oxidation in the tricarboxylic acid (TCA) cycle. To test the capacity of ccRCC to oxidize substrates in the TCA cycle, we infused C-13-labeled fuels in ccRCC patients and compared labeling patterns in tumors and adjacent kidney. After infusion with [U-C-13] glucose, ccRCCs displayed enhanced glycolytic intermediate labeling, suppressed pyruvate dehydrogenase flow, and reduced TCA cycle labeling, consistent with the Warburg effect. Comparing C-13 labeling among ccRCC, brain, and lung tumors revealed striking differences. Primary ccRCC tumors demonstrated the highest enrichment in glycolytic intermediates and lowest enrichment in TCA cycle intermediates. Among human tumors analyzed by intraoperative C-13 infusions, ccRCC is the first to demonstrate a convincing shift toward glycolytic metabolism.

机译：透明细胞肾细胞癌（CCRCC）是最常见的人肾癌形式。组织学和分子分析表明CCRCC具有显着改变的代谢。最近对肺癌和颅内恶性肿瘤的人类研究表明了三羧酸（TCA）循环中的碳水化合物氧化意外保存。为了测试CCRCC在TCA循环中氧化底物的容量，我们在CCRCC患者中脱氧了C-13标记的燃料，并比较了肿瘤和邻近肾脏的标记图案。用[U-C-13]葡萄糖输注后，CCRCC显示出增强的糖酵解中间标记，抑制丙酮酸脱氢酶流动，降低TCA循环标记，与Warburg效应一致。 C-13在CCRCC，脑和肺肿瘤中的标记揭示了惊人的差异。原发性CCRCC肿瘤证明了糖酵解中间体和TCA循环中间体中最低富集的最高富集。在通过术中C-13输注分析的人肿瘤中，CCRCC是第一个证明甘醇代谢的令人信服的转变。

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《Cell metabolism》 |2018年第5期|共10页
作者
Courtney Kevin D.; Bezwada Divya; Mashimo Tomoyuki; Pichumani Kumar; Vemireddy Vamsidhara; Funk Alexander M.; Wimberly Jennifer; McNeil Sarah S.; Kapur Payal; Lotan Yair; Margulis Vitaly; Cadeddu Jeffrey A.; Pedrosa Ivan; DeBerardinis Ralph J.; Malloy Craig R.; Bachoo Robert M.; Maher Elizabeth A.;
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Univ Texas Southwestern Med Ctr Dallas Dept Internal Med Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Childrens Med Ctr Res Inst Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Harold C Simmons Comprehens Canc Ctr Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Adv Imaging Res Ctr Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Dept Internal Med Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Adv Imaging Res Ctr Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Dept Urol Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Harold C Simmons Comprehens Canc Ctr Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Kidney Canc Program Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Dept Urol Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Dept Urol Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Dept Urol Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Kidney Canc Program Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Childrens Med Ctr Res Inst Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Dept Internal Med Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Dept Internal Med Dallas TX 75390 USA;

Univ Texas Southwestern Med Ctr Dallas Dept Internal Med Dallas TX 75390 USA;

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正文语种 eng
中图分类内分泌腺疾病及代谢病;
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1. Isotope Tracing of Human Clear Cell Renal Cell Carcinomas Demonstrates Suppressed Glucose Oxidation In Vivo [J] . Courtney Kevin D., Bezwada Divya, Mashimo Tomoyuki, Cell metabolism . 2018,第5期

机译：人透明细胞肾细胞癌的同位素描绘证明体内抑制葡萄糖氧化
2. Effects of suppressing glucose transporter-1 by an antisense oligodeoxynucleotide on the growth of human hepatocellular carcinoma cells [J] . Tian-QiLiu, JunFan, LinZhou, 国际肝胆胰疾病杂志（英文版） . 2011,第001期

机译：反义寡脱氧核苷酸抑制葡萄糖转运蛋白-1对人肝癌细胞生长的影响
3. Zinc modulates high glucose-induced apoptosis by suppressing oxidative stress in renal tubular epithelial cells [J] . ZhangX., ZhaoY., ChuQ., Biological trace element research . 2014,第2期

机译：锌通过抑制肾小管上皮细胞的氧化应激调节高糖诱导的凋亡
4. INVESTIGATION OF THE INJURY BEHAVIOR IN THERMAL THERAPY OF HUMAN RENAL CELL CARCINOMA CELLS USING A NON-ISOTHERMAL METHOD [C] . Xiaoming He, John C. Bischof HTD-vol.375-1; American Society of Mechanical Engineers(ASME) International Mechanical Engineering Congress and Exposition vol.1; 20041113-19; Anaheim,CA(US) . 2004

机译：用非等温方法研究人肾细胞癌细胞热疗过程中的损伤行为
5. Tumor Infiltrating Lymphocyte Therapy for Renal Cell Carcinoma: Methods for ex vivo Expansion and T-Cell Memory Induction [D] . Braun, Mitchell W. 2021

机译：肾细胞癌患者肿瘤浸润淋巴细胞治疗：用于脱型膨胀和T细胞记忆诱导的方法
6. Isotope tracing of human clear cell renal cell carcinomas demonstrates suppressed glucose oxidation in vivo [O] . Kevin D. Courtney, Divya Bezwada, Tomoyuki Mashimo, -1

机译：人类透明细胞肾细胞癌的同位素示踪显示体内葡萄糖氧化受到抑制
7. Isotope Tracing of Human Clear Cell Renal Cell Carcinomas Demonstrates Suppressed Glucose Oxidation In Vivo [O] . Kevin D. Courtney, Divya Bezwada, Tomoyuki Mashimo, 2018

机译：人透明细胞肾细胞癌的同位素描绘证明体内抑制葡萄糖氧化

Isotope Tracing of Human Clear Cell Renal Cell Carcinomas Demonstrates Suppressed Glucose Oxidation In Vivo

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