腫瘤微環境中麩醯胺酸耗竭對大腸直腸癌 癌症惡病質的影響

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郭蕙瑄(Hui-Hsuan Kuo) 查詢紙本館藏

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生命科學系

論文名稱

腫瘤微環境中麩醯胺酸耗竭對大腸直腸癌癌症惡病質的影響
(The effect of glutamine depletion in the tumor microenvironment on cancer cachexia in colorectal cancer)

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摘要(中)

約有60%的大腸直腸癌(Colorectal cancer , CRC)患者受到癌症惡病質(Cancer Cachexia)的影響，且為約30%患者死亡的直接原因。研究指出，與正常組織相比，腫瘤微環境中麩醯胺酸的濃度相對低下，然而，關於腫瘤微環境麩醯胺酸缺乏與大腸直腸癌引發癌症惡病質的相關研究仍有限。因此，本研究旨在於探討在麩醯胺酸匱乏條件下的大腸直腸癌細胞分泌的因子對於C2C12肌肉細胞的影響和其分子機制。研究結果顯示，人類大腸直腸癌HCT116和SW620細胞分泌的因子均可誘導C2C12肌管萎縮，且促進麩醯胺酸合成?與胺基酸轉運蛋白mRNA表達上調，推測進而調控肌肉細胞麩醯胺酸的代謝。進一步分析發現，在麩醯胺酸匱乏下，HCT116細胞分泌因子會加劇C2C12肌肉細胞萎縮，並顯著抑制C2C12肌肉細胞分化成肌管，同時更加上調C2C12肌肉細胞中麩醯胺酸合成?mRNA表達，推測可促進麩醯胺酸的合成。IL-6白血球介素為一種可誘發惡病質的細胞分泌分子。本研究發現，在麩醯胺酸匱乏下的HCT116細胞中，IL-6 mRNA表現量上升，推測IL-6蛋白質分泌量亦會上調。綜合以上，我們推測，大腸直腸癌細胞於麩醯胺酸缺乏下，可能藉由釋放IL-6來促進肌肉中的蛋白水解與加強麩醯胺酸合成，導致釋放更多的麩醯胺酸以供應癌細胞使用。

摘要(英)

Approximately 60% of colorectal cancer (CRC) patients experience cancer cachexia, which directly contributes to mortality in about 30% of cases. Studies have shown that glutamine levels in the tumor microenvironment are relatively low compared to normal tissues. However, research on the relationship between glutamine deficiency in the tumor microenvironment and CRC-induced cancer cachexia remains limited. Therefore, this study aims to investigate the effects of factors secreted by CRC cells under glutamine-deficient conditions on C2C12 muscle cells and the underlying molecular mechanisms. Our results demonstrate that factors secreted by human CRC cell lines HCT116 and SW620 induce atrophy in C2C12 myotubes and upregulate their mRNA expression of glutamine synthetase, suggesting a potential regulatory role in muscle cell glutamine metabolism. Further analysis revealed that under glutamine-deficient conditions, factors secreted by HCT116 cells exacerbate C2C12 muscle atrophy and significantly inhibit C2C12 myogenic differentiation, while further increasing the mRNA expression of glutamine synthetase in C2C12 muscle cells, potentially enhancing glutamine synthesis. Interleukin-6 (IL-6) is a cytokine known to induce cachexia. In this study, we found that IL-6 mRNA expression was upregulated in glutamine-deprived HCT116 cells, suggesting that IL-6 protein secretion may also be upregulated. In summary, our findings indicate that under glutamine-deficient conditions, CRC cells may promote protein degradation and enhance glutamine synthesis in muscle cells through IL-6 secretion, leading to increased glutamine release to support cancer cell metabolism.

關鍵字(中)

★ 癌症惡病質
★ 麩醯胺酸
★ 腫瘤微環境

關鍵字(英)

★ cancer cachexia
★ glutamine
★ tumor microenvironment

論文目次

摘要 i
Abstract ii
目錄 iii
一、緒論 Introduction 1
1-1 大腸直腸癌 (Colorectal cancer) 1
1-2 麩醯胺酸耗竭的腫瘤微環境 (Tumor microenvironment , TME) 2
1-3 癌症惡病質 (Cancer cachexia) 3
1-3-1 介紹 3
1-3-2 肌肉萎縮 (Muscle atrophy) 3
1-3-3 脂肪分解 (Adipocyte lipolysis) 4
1-4 麩醯胺酸(glutamine)的代謝 5
1-4-1 癌細胞中麩醯胺酸代謝 5
1-4-2 肌肉組織內麩醯胺酸代謝 7
1-4-3 胺基酸轉運蛋白 (Amino acid transporter) 7
1-5 肌肉生成 (Myogenesis) 8
1-6 外泌體 (Exosomes) 10
1-7 研究動機與目的 11
二、材料與方法 Materials and Methods 12
2-1 細胞株 (Cell lines) 12
2-1-1 小鼠肌纖維母細胞 : Mouse myoblast cells (C2C12) 12
2-1-2 小鼠前體脂肪細胞 : Mouse Preadipocyte Cells (3T3-L1) 12
2-1-3 人類結腸癌細胞 : Human colon cancer cells (HCT116、SW620) 13
2-2 西方墨點法 (Western blot) 13
2-2-1 Cytosol protein extraction 13
2-2-2 SDS-page (SDS - polyacrylamide gel electrophoresis) 13
2-2-3 Transfer 14
2-2-4 Blocking及抗體辨識 14
2-3 免疫螢光染色(Immunofluorescence, IF) 14
2-4 RNA萃取 15
2-5反轉錄作用(Reverse Transcription, RT) 16
2-6 即時定量聚合?連鎖反應(Quantitative Real-Time Polymerase Chain Reaction, qRT-PCR) 16
2-7 麩醯胺酸測定 17
2-8 外泌體萃取 17
三、實驗結果 Results 18
3-1 HCT116的conditioned medium(CM)誘導C2C12肌管萎縮並調節其麩醯胺酸代謝 18
3-2 SW620的CM促使C2C12肌管萎縮並影響其麩醯胺酸代謝 19
3-3 HCT116 CM造成的C2C12肌管萎縮與麩醯胺酸代謝改變並非肇於CM中的低麩醯胺酸濃度 20
3-4 SW620分泌的因子促使C2C12肌管萎縮並調節其麩醯胺酸代謝 21
3-5 HCT116細胞在麩醯胺酸耗竭狀態下誘導C2C12肌管萎縮且促進麩醯胺酸代謝 22
3-6 HCT116細胞在麩醯胺酸缺乏狀態下所釋放的因子誘導C2C12肌管萎縮及促進麩醯胺酸代謝改變並非肇於CM中的低麩醯胺酸濃度 23
3-7 SW620細胞於麩醯胺酸缺乏狀態下分泌的因子對C2C12造成的影響 24
3-8 HCT116細胞在麩醯胺酸耗竭狀態下分泌的外泌體不會導致C2C12肌管萎縮 25
3-9 大腸直腸癌細胞分泌的因子抑制C2C12肌肉細胞的分化 26
3-10大腸直腸癌細胞誘導C2C12肌肉細胞分化過程中麩醯胺酸的代謝 27
3-11 大腸直腸癌細胞釋放的因子可能促使3T3-L1脂肪細胞分解 28
四、討論 Discussion 30
4-1 大腸直腸癌細胞釋放的因子對C2C12肌肉細胞的影響 30
4-2 麩醯胺酸匱乏條件下大腸直腸癌細胞分泌因子對C2C12肌肉細胞的影響 31
4-3 大腸直腸癌細胞分泌的因子對 C2C12 肌肉細胞分化的調控影響 33
4-4 大腸直腸癌細胞在麩醯胺酸匱乏下分泌因子對 C2C12 肌肉細胞麩醯胺酸代謝調控的影響 34
4-5 大腸直腸癌細胞在不同條件下分泌的物質對3T3-L1脂肪細胞產生的影響 35
4-6 結論 36
五、圖表 Figures 37
Fig 1. HCT116的CM對於C2C12造成的影響 38
Fig 2. SW620的CM對於C2C12造成的影響 41
Fig 3. HCT116細胞分泌的因子對C2C12造成的影響 44
Fig 4. SW620細胞釋放的因子對C2C12的影響 47
Fig 5. HCT116細胞在正常情況及麩醯胺酸耗竭狀態下的CM對於C2C12 肌肉細胞的影響 50
Fig 6. HCT116細胞在麩醯胺酸耗竭狀態下釋放的因子對C2C12的影響 52
Fig 7. SW620細胞在正常情況及麩醯胺酸耗竭狀態下的CM對於C2C12的影響 55
Fig 8. HCT116細胞分泌的外泌體對C2C12肌肉細胞的影響 58
Fig 9. HCT116細胞分泌的因子對於C2C12肌肉生成(Myogenesis)的影響 60
Fig 10. SW620細胞分泌的因子對於C2C12肌肉生成(Myogenesis)的影響 63
Fig 11. HCT116細胞和SW620細胞分泌的因子對於C2C12肌肉細胞中麩醯胺酸代謝的影響 66
Fig 12. HCT116細胞和SW620細胞分泌的因子對3T3-L1脂肪細胞的影響 69
Fig 13. 模式圖 70
六、參考文獻 Reference 71
七、附錄 78
附錄一、抗體 78
附錄二、Primer list 79

參考文獻

Abels, E. R., & Breakefield, X. O. (2016). Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake. Cell Mol Neurobiol, 36(3), 301-312. https://doi.org/10.1007/s10571-016-0366-z
Altman, B. J., Stine, Z. E., & Dang, C. V. (2016). From Krebs to clinic: glutamine metabolism to cancer therapy. Nat Rev Cancer, 16(10), 619-634. https://doi.org/10.1038/nrc.2016.71
Anker, M. S., Holcomb, R., Muscaritoli, M., von Haehling, S., Haverkamp, W., Jatoi, A., Morley, J. E., Strasser, F., Landmesser, U., Coats, A. J. S., & Anker, S. D. (2019). Orphan disease status of cancer cachexia in the USA and in the European Union: a systematic review. J Cachexia Sarcopenia Muscle, 10(1), 22-34. https://doi.org/10.1002/jcsm.12402
Argiles, J. M., Busquets, S., Toledo, M., & Lopez-Soriano, F. J. (2009). The role of cytokines in cancer cachexia. Curr Opin Support Palliat Care, 3(4), 263-268. https://doi.org/10.1097/SPC.0b013e3283311d09
Awad, S., Skipper, W., Vostrejs, W., Ozorowski, K., Min, K., Pfuhler, L., Mehta, D., & Cooke, A. (2024). The YBX3 RNA-binding protein posttranscriptionally controls SLC1A5 mRNA in proliferating and differentiating skeletal muscle cells. J Biol Chem, 300(2), 105602. https://doi.org/10.1016/j.jbc.2023.105602
Baghban, R., Roshangar, L., Jahanban-Esfahlan, R., Seidi, K., Ebrahimi-Kalan, A., Jaymand, M., Kolahian, S., Javaheri, T., & Zare, P. (2020). Tumor microenvironment complexity and therapeutic implications at a glance. Cell Communication and Signaling, 18(1), 59. https://doi.org/10.1186/s12964-020-0530-4
Baracos, V. E., Martin, L., Korc, M., Guttridge, D. C., & Fearon, K. C. H. (2018). Cancer-associated cachexia. Nat Rev Dis Primers, 4, 17105. https://doi.org/10.1038/nrdp.2017.105
Bhaskar, P. T., & Hay, N. (2007). The Two TORCs and Akt. Developmental Cell, 12(4), 487-502. https://doi.org/10.1016/j.devcel.2007.03.020
Bhutia, Y. D., & Ganapathy, V. (2016). Glutamine transporters in mammalian cells and their functions in physiology and cancer. Biochim Biophys Acta, 1863(10), 2531-2539. https://doi.org/10.1016/j.bbamcr.2015.12.017
Bilodeau, P. A., Coyne, E. S., & Wing, S. S. (2016). The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation. Am J Physiol Cell Physiol, 311(3), C392-403. https://doi.org/10.1152/ajpcell.00125.2016
Biolo, G., Fleming, R. Y., Maggi, S. P., & Wolfe, R. R. (1995). Transmembrane transport and intracellular kinetics of amino acids in human skeletal muscle. Am J Physiol, 268(1 Pt 1), E75-84. https://doi.org/10.1152/ajpendo.1995.268.1.E75
Bodine, S. C., & Baehr, L. M. (2014). Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am J Physiol Endocrinol Metab, 307(6), E469-484. https://doi.org/10.1152/ajpendo.00204.2014
Bodineau, C., Tome, M., Courtois, S., Costa, A. S. H., Sciacovelli, M., Rousseau, B., Richard, E., Vacher, P., Parejo-Perez, C., Bessede, E., Varon, C., Soubeyran, P., Frezza, C., Murdoch, P. D. S., Villar, V. H., & Duran, R. V. (2021). Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis. Nat Commun, 12(1), 4814. https://doi.org/10.1038/s41467-021-25079-4
Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 74(3), 229-263. https://doi.org/10.3322/caac.21834
Buckingham, M. (2007). Skeletal muscle progenitor cells and the role of Pax genes. C R Biol, 330(6-7), 530-533. https://doi.org/10.1016/j.crvi.2007.03.015
Campos, F. G. (2017). Colorectal cancer in young adults: A difficult challenge. World J Gastroenterol, 23(28), 5041-5044. https://doi.org/10.3748/wjg.v23.i28.5041
Chal, J., & Pourquie, O. (2017). Making muscle: skeletal myogenesis in vivo and in vitro. Development, 144(12), 2104-2122. https://doi.org/10.1242/dev.151035
Choi, Y. K., & Park, K. G. (2018). Targeting Glutamine Metabolism for Cancer Treatment. Biomol Ther (Seoul), 26(1), 19-28. https://doi.org/10.4062/biomolther.2017.178
Collins, C. A., Gnocchi, V. F., White, R. B., Boldrin, L., Perez-Ruiz, A., Relaix, F., Morgan, J. E., & Zammit, P. S. (2009). Integrated functions of Pax3 and Pax7 in the regulation of proliferation, cell size and myogenic differentiation. PLoS One, 4(2), e4475. https://doi.org/10.1371/journal.pone.0004475
Curthoys, N. P., & Watford, M. (1995). Regulation of glutaminase activity and glutamine metabolism. Annu Rev Nutr, 15, 133-159. https://doi.org/10.1146/annurev.nu.15.070195.001025
Di, W., Zhang, W., Zhu, B., Li, X., Tang, Q., & Zhou, Y. (2021). Colorectal cancer prompted adipose tissue browning and cancer cachexia through transferring exosomal miR-146b-5p. J Cell Physiol, 236(7), 5399-5410. https://doi.org/10.1002/jcp.30245
Eagle, H. (1955). Nutrition needs of mammalian cells in tissue culture. Science, 122(3168), 501-514. https://doi.org/10.1126/science.122.3168.501
Fan, S. J., Kroeger, B., Marie, P. P., Bridges, E. M., Mason, J. D., McCormick, K., Zois, C. E., Sheldon, H., Khalid Alham, N., Johnson, E., Ellis, M., Stefana, M. I., Mendes, C. C., Wainwright, S. M., Cunningham, C., Hamdy, F. C., Morris, J. F., Harris, A. L., Wilson, C., & Goberdhan, D. C. (2020). Glutamine deprivation alters the origin and function of cancer cell exosomes. Embo j, 39(16), e103009. https://doi.org/10.15252/embj.2019103009
Fearon, K., Strasser, F., Anker, S. D., Bosaeus, I., Bruera, E., Fainsinger, R. L., Jatoi, A., Loprinzi, C., MacDonald, N., Mantovani, G., Davis, M., Muscaritoli, M., Ottery, F., Radbruch, L., Ravasco, P., Walsh, D., Wilcock, A., Kaasa, S., & Baracos, V. E. (2011). Definition and classification of cancer cachexia: an international consensus. Lancet Oncol, 12(5), 489-495. https://doi.org/10.1016/s1470-2045(10)70218-7
Gandhi, A. Y., Yu, J., Gupta, A., Guo, T., Iyengar, P., & Infante, R. E. (2022). Cytokine-Mediated STAT3 Transcription Supports ATGL/CGI-58-Dependent Adipocyte Lipolysis in Cancer Cachexia. Front Oncol, 12, 841758. https://doi.org/10.3389/fonc.2022.841758
Garber, A. J., Karl, I. E., & Kipnis, D. M. (1976). Alanine and glutamine synthesis and release from skeletal muscle. I. Glycolysis and amino acid release. J Biol Chem, 251(3), 826-835.
Gonzalez, A., Hall, M. N., Lin, S. C., & Hardie, D. G. (2020). AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control. Cell Metab, 31(3), 472-492. https://doi.org/10.1016/j.cmet.2020.01.015
Hensley, C. T., Wasti, A. T., & DeBerardinis, R. J. (2013). Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Invest, 123(9), 3678-3684. https://doi.org/10.1172/jci69600
Hernandez-Hernandez, J. M., Garcia-Gonzalez, E. G., Brun, C. E., & Rudnicki, M. A. (2017). The myogenic regulatory factors, determinants of muscle development, cell identity and regeneration. Semin Cell Dev Biol, 72, 10-18. https://doi.org/10.1016/j.semcdb.2017.11.010
Huang, F., Zhao, Y., Zhao, J., Wu, S., Jiang, Y., Ma, H., & Zhang, T. (2014). Upregulated SLC1A5 promotes cell growth and survival in colorectal cancer. Int J Clin Exp Pathol, 7(9), 6006-6014.
Huang, Y.-F., Wang, Y., & Watford, M. (2007). Glutamine Directly Downregulates Glutamine Synthetase Protein Levels in Mouse C2C12 Skeletal Muscle Myotubes12. The Journal of Nutrition, 137(6), 1357-1362. https://doi.org/https://doi.org/10.1093/jn/137.6.1357
Huot, J. R., Novinger, L. J., Pin, F., & Bonetto, A. (2020). HCT116 colorectal liver metastases exacerbate muscle wasting in a mouse model for the study of colorectal cancer cachexia. Dis Model Mech, 13(1). https://doi.org/10.1242/dmm.043166
Isesele, P. O., & Mazurak, V. C. (2021). Regulation of Skeletal Muscle Satellite Cell Differentiation by Omega-3 Polyunsaturated Fatty Acids: A Critical Review. Front Physiol, 12, 682091. https://doi.org/10.3389/fphys.2021.682091
Jang, Y. N., & Baik, E. J. (2013). JAK-STAT pathway and myogenic differentiation. Jakstat, 2(2), e23282. https://doi.org/10.4161/jkst.23282
Jing, X., Yang, F., Shao, C., Wei, K., Xie, M., Shen, H., & Shu, Y. (2019). Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer, 18(1), 157. https://doi.org/10.1186/s12943-019-1089-9
Kalluri, R., & LeBleu, V. S. (2020). The biology, function, and biomedical applications of exosomes. Science, 367(6478). https://doi.org/10.1126/science.aau6977
Khalil, R. (2018). Ubiquitin-Proteasome Pathway and Muscle Atrophy. Adv Exp Med Biol, 1088, 235-248. https://doi.org/10.1007/978-981-13-1435-3_10
Komander, D. (2009). The emerging complexity of protein ubiquitination. Biochem Soc Trans, 37(Pt 5), 937-953. https://doi.org/10.1042/bst0370937
Kuhn, K. S., Schuhmann, K., Stehle, P., Darmaun, D., & Furst, P. (1999). Determination of glutamine in muscle protein facilitates accurate assessment of proteolysis and de novo synthesis-derived endogenous glutamine production. Am J Clin Nutr, 70(4), 484-489. https://doi.org/10.1093/ajcn/70.4.484
Labow, B. I., Souba, W. W., & Abcouwer, S. F. (2001). Mechanisms Governing the Expression of the Enzymes of Glutamine Metabolism—Glutaminase and Glutamine Synthetase. The Journal of Nutrition, 131(9), 2467S-2474S. https://doi.org/https://doi.org/10.1093/jn/131.9.2467S
Leowattana, W., Leowattana, P., & Leowattana, T. (2023). Systemic treatment for metastatic colorectal cancer. World J Gastroenterol, 29(10), 1569-1588. https://doi.org/10.3748/wjg.v29.i10.1569
Li, Y. P., Chen, Y., John, J., Moylan, J., Jin, B., Mann, D. L., & Reid, M. B. (2005). TNF-alpha acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. Faseb j, 19(3), 362-370. https://doi.org/10.1096/fj.04-2364com
Malla, J., Zahra, A., Venugopal, S., Selvamani, T. Y., Shoukrie, S. I., Selvaraj, R., Dhanoa, R. K., Hamouda, R. K., & Mostafa, J. (2022). What Role Do Inflammatory Cytokines Play in Cancer Cachexia? Cureus, 14(7), e26798. https://doi.org/10.7759/cureus.26798
Miao, C., Zhang, W., Feng, L., Gu, X., Shen, Q., Lu, S., Fan, M., Li, Y., Guo, X., Ma, Y., Liu, X., Wang, H., & Zhang, X. (2021). Cancer-derived exosome miRNAs induce skeletal muscle wasting by Bcl-2-mediated apoptosis in colon cancer cachexia. Mol Ther Nucleic Acids, 24, 923-938. https://doi.org/10.1016/j.omtn.2021.04.015
Nicklin, P., Bergman, P., Zhang, B., Triantafellow, E., Wang, H., Nyfeler, B., Yang, H., Hild, M., Kung, C., Wilson, C., Myer, V. E., MacKeigan, J. P., Porter, J. A., Wang, Y. K., Cantley, L. C., Finan, P. M., & Murphy, L. O. (2009). Bidirectional transport of amino acids regulates mTOR and autophagy. Cell, 136(3), 521-534. https://doi.org/10.1016/j.cell.2008.11.044
Nurjhan, N., Bucci, A., Perriello, G., Stumvoll, M., Dailey, G., Bier, D. M., Toft, I., Jenssen, T. G., & Gerich, J. E. (1995). Glutamine: a major gluconeogenic precursor and vehicle for interorgan carbon transport in man. J Clin Invest, 95(1), 272-277. https://doi.org/10.1172/jci117651
Pan, M., Reid, M. A., Lowman, X. H., Kulkarni, R. P., Tran, T. Q., Liu, X., Yang, Y., Hernandez-Davies, J. E., Rosales, K. K., Li, H., Hugo, W., Song, C., Xu, X., Schones, D. E., Ann, D. K., Gradinaru, V., Lo, R. S., Locasale, J. W., & Kong, M. (2016). Regional glutamine deficiency in tumours promotes dedifferentiation through inhibition of histone demethylation. Nature Cell Biology, 18(10), 1090-1101. https://doi.org/10.1038/ncb3410
Pedersen, K. S., Gatto, F., Zerahn, B., Nielsen, J., Pedersen, B. K., Hojman, P., & Gehl, J. (2020). Exercise-Mediated Lowering of Glutamine Availability Suppresses Tumor Growth and Attenuates Muscle Wasting. iScience, 23(4), 100978. https://doi.org/10.1016/j.isci.2020.100978
Prado, B. L., & Qian, Y. (2019). Anti-cytokines in the treatment of cancer cachexia. Ann Palliat Med, 8(1), 67-79. https://doi.org/10.21037/apm.2018.07.06
Ruan, G. T., Xie, H. L., Yuan, K. T., Lin, S. Q., Zhang, H. Y., Liu, C. A., Shi, J. Y., Ge, Y. Z., Song, M. M., Hu, C. L., Zhang, X. W., Liu, X. Y., Yang, M., Wang, K. H., Zheng, X., Chen, Y., Hu, W., Cong, M. H., Zhu, L. C., . . . Shi, H. P. (2023). Prognostic value of systemic inflammation and for patients with colorectal cancer cachexia. J Cachexia Sarcopenia Muscle, 14(6), 2813-2823. https://doi.org/10.1002/jcsm.13358
Ruers, T., & Bleichrodt, R. P. (2002). Treatment of liver metastases, an update on the possibilities and results. Eur J Cancer, 38(7), 1023-1033. https://doi.org/10.1016/s0959-8049(02)00059-x
Sakata, T., Ferdous, G., Tsuruta, T., Satoh, T., Baba, S., Muto, T., Ueno, A., Kanai, Y., Endou, H., & Okayasu, I. (2009). L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer. Pathol Int, 59(1), 7-18. https://doi.org/10.1111/j.1440-1827.2008.02319.x
Schmidt, M., Schuler, S. C., Huttner, S. S., von Eyss, B., & von Maltzahn, J. (2019). Adult stem cells at work: regenerating skeletal muscle. Cell Mol Life Sci, 76(13), 2559-2570. https://doi.org/10.1007/s00018-019-03093-6
Sener, A., & Malaisse, W. J. (1980). L-leucine and a nonmetabolized analogue activate pancreatic islet glutamate dehydrogenase. Nature, 288(5787), 187-189. https://doi.org/10.1038/288187a0
Setiawan, T., Sari, I. N., Wijaya, Y. T., Julianto, N. M., Muhammad, J. A., Lee, H., Chae, J. H., & Kwon, H. Y. (2023). Cancer cachexia: molecular mechanisms and treatment strategies. J Hematol Oncol, 16(1), 54. https://doi.org/10.1186/s13045-023-01454-0
Tajbakhsh, S. (2009). Skeletal muscle stem cells in developmental versus regenerative myogenesis. J Intern Med, 266(4), 372-389. https://doi.org/10.1111/j.1365-2796.2009.02158.x
Urabe, F., Kosaka, N., Ito, K., Kimura, T., Egawa, S., & Ochiya, T. (2020). Extracellular vesicles as biomarkers and therapeutic targets for cancer. Am J Physiol Cell Physiol, 318(1), C29-c39. https://doi.org/10.1152/ajpcell.00280.2019
Valderrama-Trevino, A. I., Barrera-Mera, B., Ceballos-Villalva, J. C., & Montalvo-Jave, E. E. (2017). Hepatic Metastasis from Colorectal Cancer. Euroasian J Hepatogastroenterol, 7(2), 166-175. https://doi.org/10.5005/jp-journals-10018-1241
van Geldermalsen, M., Wang, Q., Nagarajah, R., Marshall, A. D., Thoeng, A., Gao, D., Ritchie, W., Feng, Y., Bailey, C. G., Deng, N., Harvey, K., Beith, J. M., Selinger, C. I., O′Toole, S. A., Rasko, J. E., & Holst, J. (2016). ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer. Oncogene, 35(24), 3201-3208. https://doi.org/10.1038/onc.2015.381
Wang, Y., Dong, Z., An, Z., & Jin, W. (2024). Cancer cachexia: Focus on cachexia factors and inter-organ communication. Chin Med J (Engl), 137(1), 44-62. https://doi.org/10.1097/cm9.0000000000002846
Wu, C., Zhu, M., Lu, Z., Zhang, Y., Li, L., Li, N., Yin, L., Wang, H., Song, W., & Xu, H. (2021). L-carnitine ameliorates the muscle wasting of cancer cachexia through the AKT/FOXO3a/MaFbx axis. Nutr Metab (Lond), 18(1), 98. https://doi.org/10.1186/s12986-021-00623-7
Yoo, H. C., Yu, Y. C., Sung, Y., & Han, J. M. (2020). Glutamine reliance in cell metabolism. Exp Mol Med, 52(9), 1496-1516. https://doi.org/10.1038/s12276-020-00504-8
Zammit, P. S. (2017). Function of the myogenic regulatory factors Myf5, MyoD, Myogenin and MRF4 in skeletal muscle, satellite cells and regenerative myogenesis. Semin Cell Dev Biol, 72, 19-32. https://doi.org/10.1016/j.semcdb.2017.11.011
Zanou, N., & Gailly, P. (2013). Skeletal muscle hypertrophy and regeneration: interplay between the myogenic regulatory factors (MRFs) and insulin-like growth factors (IGFs) pathways. Cell Mol Life Sci, 70(21), 4117-4130. https://doi.org/10.1007/s00018-013-1330-4
Zechner, R., Kienesberger, P. C., Haemmerle, G., Zimmermann, R., & Lass, A. (2009). Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. J Lipid Res, 50(1), 3-21. https://doi.org/10.1194/jlr.R800031-JLR200
Zhang, J., Pavlova, N. N., & Thompson, C. B. (2017). Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine. Embo j, 36(10), 1302-1315. https://doi.org/10.15252/embj.201696151
Zierath, J. R., & Hawley, J. A. (2004). Skeletal muscle fiber type: influence on contractile and metabolic properties. PLoS Biol, 2(10), e348. https://doi.org/10.1371/journal.pbio.0020348

指導教授

范世榮(Shih-Jung Fan)

審核日期

2025-3-27

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