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研究生: 王之璇
Wang, Chih-Husan
論文名稱: Aspirin抑制肥胖相關發炎因子促進乳癌細胞生長之探討
The effect of aspirin inhibits obesity-related inflammatory mediators promoting the growth of breast cancer cell
指導教授: 謝佳倩
Hsieh, Chia-Chien
學位類別: 碩士
Master
系所名稱: 人類發展與家庭學系
Department of Human Development and Family Studies
論文出版年: 2017
畢業學年度: 105
語文別: 中文
論文頁數: 118
中文關鍵詞: Aspirin肥胖乳癌發炎反應
英文關鍵詞: macrophages
DOI URL: https://doi.org/10.6345/NTNU202203069
論文種類: 學術論文
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  • 肥胖為一全球性的健康議題,流行病學研究顯示肥胖會增加女性乳癌的發生率且具有較差的預後。肥胖者的脂肪組織中有多種免疫細胞浸潤,其中以巨噬細胞數量較多,形成低度慢性發炎反應,增加發炎性細胞激素的分泌,並伴隨血管新生因子的增加及脂肪激素的失調,皆有利於腫瘤的生長。而在腫瘤的微環境中,乳癌細胞透過誘導腫瘤相關巨噬細胞來達到促進腫瘤生長及轉移的效果。Aspirin為目前廣泛使用的非固醇類抗發炎藥物,也被證實具有癌症預防的作用,然而aspirin對脂肪、乳癌及免疫細胞間之交互作用的影響仍不明確。本研究目的為探討aspirin是否能抑制脂肪細胞的發炎現象,並調節巨噬細胞的免疫反應,進而抑制乳癌細胞的生長。
    第一部份,建立以TNF-α、LPS或RAW264.7巨噬細胞條件培養液 (RAW 264.7 conditioned meium, RAW-CM)誘發3T3-L1脂肪細胞發炎的實驗模式,結果顯示aspirin能顯著降低MCP-1、IL-6、IL-1β及PAI-1的分泌。第二部分建立肥胖模式下4T1細胞生長與移行能力的實驗,結果顯示3T3-L1脂肪細胞條件培養液 (Adipocyte conditioned medium, Ad-CM)會促進乳癌細胞的生長和移行,而aspirin能發揮抑制的功效。另外在Ad-CM的代謝體分析中發現3T3-L1分化為脂肪細胞後對胺基酸的利用及蛋白質合成的需求增加,脂質代謝及氧化壓力隨之上升,而在分化過程給予aspirin的處理可顯著降低Ad-CM中脂質代謝相關的2-Hydroxycaproic acid與增加氧化壓力的hydroxyphenyllactic acid含量,表示aspirin能阻斷3T3-L1脂肪細胞分化的代謝變化。在Ad-CM脂肪酸相對定量分析中3T3-L1在分化過程中給予aspirin的處理,可顯著降低C16:1、C18:1、C18:2、C20:4和C24:1,顯示aspirin減少CM中游離脂肪酸的含量。第三部分,探討巨噬細胞與乳癌細胞間的關係,在LPS刺激RAW264.7所收集的CM培養4T1細胞可抑制細胞生長,反之沒有刺激下所收集的CM則會促進4T1細胞的生長與移行、VEGF、PAI-1、TNF-α和IL-6的分泌,且aspirin處理下具有抑制的作用。接著在RAW-CM的代謝體分析,發現無LPS刺激的CM中2-ketohexanoic acid/ketoleucine、lactate和arginine等可能和肥胖相關發炎及促進癌症生長的物質顯著上升,而LPS刺激後整體的能量代謝增加,而aspirin的處理對LPS刺激之RAW-CM影響仍不明確。第四部分,在4T1細胞與RAW264.7細胞共培養模式中,與4T1細胞共培養後的RAW264.7細胞傾向免疫抑制的M2型,且aspirin處理能增加CD11c (M1型)並降低CD206 (M2型)的表現。
    綜合而論,aspirin能降低脂肪細胞的發炎反應,及抑制脂肪細胞和巨噬細胞促進乳癌細胞生長的作用,尤其在腫瘤微環境下,aspirin可降低有利於癌細胞生長的細胞激素並調節RAW264.7巨噬細胞之表型趨向,aspirin由影響數種細胞來調節肥胖相關的炎症反應以達到抗腫瘤的功效。

    Epidemiological studies have shown that obesity increases the incidence of breast cancer and leads the worse prognosis. The adipose tissue of obese individuals generally accompanies macrophages infiltration and inflammatory cytokines secretion. The microenviroment with a chronic, low-grade inflammation, angiogenesis and adipokine dysregulation provides an ideal condition for tumor development, growth and migration. Moreover, cancer cells secret mediators attract macrophages and other immune cells to support tumor development and metastasis. Aspirin is a non-steroidal anti-inflammatory drug (NSAID), has been known as a chemopreventive agent against several types of cancer. However, the effect of aspirin on the interaction among adipocyte, macrophage and breast cancer cell is still elusive. The aim of this work is to investigate whether aspirin can inhibit inflammatory respond of 3T3-L1 adipocyte, regulate immune respond of RAW 264.7 macrophage, and then inhibit growth of 4T1 breast cancer cell.
    First, we established an inflammatory model of 3T3-L1 adipocyte by TNF-α, LPS and RAW 264.7 macrophage conditioned meium (RAW-CM) stimulation. The results had shown that aspirin significantly inhibited MCP-1、IL-6、IL-1β and PAI-1 productions in 3T3-L1 adipocytes. Second, in the obesity-associated model of 4T1 breast cancer cells, 3T3-L1 adipocyte conditioned meium (Ad-CM) treatment significantly promoted 4T1 cell growth and migration. Futhermore, the Ad-CM was collected from aspirin treatment during 3T3-L1 differentication, resulted to inhibit the cell viability of 4T1 cell. In addition, in the result of metabolic analysis of Ad-CM, protein synthesis and oxidative stress were increased in mature 3T3-L1 adipocytes. Aspirin treatment reduced oxidative stress in Ad-CM and reversed the metabolic chage of adipocytes. In the relative fatty acid quantitation analysis of Ad-CM, aspirin diminished free fatty acid C16:1, C18:1, C18:2, C20:4 and C24:1. Third, in the model of 4T1 cell cultured in RAW-CM, 4T1 cells were treated with RAW-CM with LPS stimulation significantly inhibited cell growth and migration. On the contrary, 4T1 cells were cultured in RAW-CM without stimulation resulted to promote cell growth, migration and cytokine VEGF, PAI-1, TNF- and IL-6 secretions, while aspirin treatment exerted an inhibitory effects. Additionally, molecules related to obesity-associatd inflammation and tumor development were found in RAW-CM without stimulation by the metabolic analysis, while the effect of aspirin was not clear in the CM with LPS stimulation. Finally, aspirin significantly decreased CD206 (M2) of macrophages while CD11c (M1) was increased in co-culture of 4T1 and RAW264.7 cells, suggested that aspirin blunt tumor suppressed environment through regulating macrophages M1/M2 subtypes.
    In conclusion, aspirin inhibited the inflammatory respond of adipocyte and the tumor-promoting effects of adipocytes and macrophages. This study indicated that aspirin breaks the crosstalk among 3T3-L1 adipocytes, RAW264.7 macrophages and 4T1 breast cancer cells, exerted anti-tumor effects by ameliorating obesity-associated inflammation.

    目錄 第一章 文獻探討 1 第一節 肥胖 1 第二節 乳癌 9 第三節 Aspirin 14 第四節 研究工具 17 第二章 研究假說與目的 23 第一節 研究假說 23 第二節 研究目的 23 第三節 實驗架構 24 第三章 實驗材料與方法 25 第一節 實驗藥品來源 25 第二節 實驗細胞來源 25 第三節 實驗儀器設備與耗材 25 第四節 實驗材料與方法 27 一、3T3-L1 脂肪細胞的培養與誘發發炎反應的模式 27 二、建立肥胖相關微環境下對4T1乳癌細胞生長與移行的影響 31 三、建立4T1乳癌細胞與RAW264.7巨噬細胞培養液的研究模式 34 四、建立4T1乳癌細胞與RAW264.7巨噬細胞共培養的研究模式 38 第五節 統計分析 39 第四章 實驗結果 40 第一節 誘發3T3-L1脂肪細胞發炎反應的模式 40 一、 Aspirin對TNF-α和LPS誘發3T3-L1脂肪細胞細胞激素之影響 42 二、 Aspirin對3T3-L1脂肪細胞培養在RAW264.7細胞培養液下細胞激素之影響 45 第二節 4T1乳癌細胞與3T3-L1脂肪細胞培養液的研究模式 47 一、 3T3-L1脂肪細胞培養液對4T1細胞生長的影響 47 二、 3T3-L1細胞培養液的小分子代謝體分析 48 三、 3T3-L1細胞培養液的脂肪酸相對定量分析 54 四、 肥胖模式下Aspirin對4T1細胞移行能力的影響 57 第三節 4T1乳癌細胞與RAW264.7巨噬細胞培養液的研究模式 60 一、 4T1細胞培養在RAW264.7細胞培養液對細胞生長的影響 60 二、 Aspirin對4T1細胞在RAW 264.7細胞培養液下細胞生長的影響 62 三、 4T1細胞培養在RAW264.7細胞培養液對移行能力的影響 63 四、 Aspirin對4T1細胞培養在RAW264.7細胞培養液下移行能力的影響 65 五、 RAW264.7細胞培養液的小分子代謝體分析 67 六、 Aspirin對4T1細胞在RAW 264.7細胞培養液下細胞激素的影響 72 第四節 4T1乳癌細胞與RAW264.7巨噬細胞共培養的研究模式 76 一、 4T1細胞與RAW 264.7細胞共培養對M1/M2表型的影響 76 二、 Aspirin對4T1細胞與RAW264.7細胞共培養模式下細胞激素的影響 79 第五章 討論 82 第一節 Aspirin對3T3-L1脂肪細胞發炎性細胞激素的影響 82 第二節 4T1乳癌細胞與3T3-L1脂肪細胞培養液的研究模式 83 一、 3T3-L1脂肪細胞培養液對4T1細胞生長和移行能力的影響 83 二、 3T3-L1細胞分化對代謝體組成的影響 84 三、 Aspirin對3T3-L1脂肪細胞分化過程中代謝體組成的影響 84 四、 3T3-L1細胞分化對脂肪酸組成的影響 86 五、 Aspirin對3T3-L1脂肪細胞分化過程中脂肪酸組成的影響 87 六、肥胖模式下Aspirin對4T1細胞移行能力的影響 88 第三節 4T1乳癌細胞與RAW264.7巨噬細胞培養液的研究模式 88 一、 4T1細胞培養在RAW264.7細胞培養液對細胞生長和移行能力的影響 88 二、 Aspirin對4T1細胞培養在RAW 264.7細胞培養液下細胞生長及移行能力的影響 89 三、 RAW264.7細胞給予LPS刺激及aspirin的處理對代謝體組成的影響 90 四、 Aspirin對4T1細胞在RAW 264.7細胞培養液下細胞激素的影響 93 第四節 4T1乳癌細胞與RAW264.7巨噬細胞共培養的研究模式 94 一、 4T1細胞與RAW264.7細胞在共培養下對M1/M2表型的影響 94 二、 Aspirin對4T1細胞與RAW264.7細胞共培養模式下細胞激素的影響 95 第六章 結論 96 第七章 參考文獻 98

    Adams, S. H. (2011). Emerging perspectives on essential amino acid metabolism in obesity and the insulin-resistant state. Adv Nutr, 2(6), 445-456. doi: 10.3945/an.111.000737
    Alegre, M. M., Knowles, M. H., Robison, R. A., & O'Neill, K. L. (2013). Mechanics behind Breast Cancer Prevention - Focus on Obesity, Exercise and Dietary Fat. Asian Pacific Journal of Cancer Prevention, 14(4), 2207-2212. doi: 10.7314/apjcp.2013.14.4.2207
    Allavena, P., Garlanda, C., Borrello, M. G., Sica, A., & Mantovani, A. (2008). Pathways connecting inflammation and cancer. Curr Opin Genet Dev, 18(1), 3-10. doi: 10.1016/j.gde.2008.01.003
    Amling, C. L., Riffenburgh, R. H., Sun, L., Moul, J. W., Lance, R. S., Kusuda, L., & McLeod, D. G. (2004). Pathologic variables and recurrence rates as related to obesity and race in men with prostate cancer undergoing radical prostatectomy. J Clin Oncol, 22(3), 439-445. doi: 10.1200/jco.2004.03.132
    An, Y., Liu, K., Zhou, Y., & Liu, B. (2009). Salicylate inhibits macrophage-secreted factors induced adipocyte inflammation and changes of adipokines in 3T3-L1 adipocytes. Inflammation, 32(5), 296-303. doi: 10.1007/s10753-009-9135-1
    Azrad, M., Turgeon, C., & Demark-Wahnefried, W. (2013). Current evidence linking polyunsaturated Fatty acids with cancer risk and progression. Front Oncol, 3, 224. doi:10.3389/fonc.2013.00224
    Balaban, S., Shearer, R. F., Lee, L. S., van Geldermalsen, M., Schreuder, M., Shtein, H. C., & Hoy, A. J. (2017). Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration. Cancer Metab, 5, 1. doi:10.1186/s40170-016-0163-7
    Balkwill, F. (2009). Tumour necrosis factor and cancer. Nat Rev Cancer, 9(5), 361-371. doi:10.1038/nrc2628
    Bastard, J. P., & Piéroni, L. (1999). Plasma plasminogen activator inhibitor 1, insulin resistance and android obesity. Biomedicine & Pharmacotherapy, 53(10), 455-461. doi: http://dx.doi.org/10.1016/S0753-3322(00)88103-2
    Beger, R. D. (2013). A review of applications of metabolomics in cancer. Metabolites, 3(3), 552-574. doi: 10.3390/metabo3030552
    Benavides, M. A., Oelschlager, D. K., Zhang, H. G., Stockard, C. R., Vital-Reyes, V. S., Katkoori, V. R., & Grizzle, W. E. (2007). Methionine inhibits cellular growth dependent on the p53 status of cells. Am J Surg, 193(2), 274-283. doi: 10.1016/j.amjsurg.2006.07.016
    Bingle, L., Brown, N. J., & Lewis, C. E. (2002). The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol, 196(3), 254-265. doi: 10.1002/path.1027
    Bierie, B., & Moses, H. L. (2010). Transforming growth factor beta (TGF-beta) and inflammation in cancer. Cytokine Growth Factor Rev, 21(1), 49-59. doi:10.1016/j.cytogfr.2009.11.008
    Biswas, S. K., Gangi, L., Paul, S., Schioppa, T., Saccani, A., Sironi, M., & Sica, A. (2006). A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood, 107(5), 2112-2122. doi:10.1182/blood-2005-01-0428
    Block, R. C., Abdolahi, A., Smith, B., Meednu, N., Thevenet-Morrison, K., Cai, X., & Georas, S. (2013). Effects of low-dose aspirin and fish oil on platelet function and NF-kappaB in adults with diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids, 89(1), 9-18. doi: 10.1016/j.plefa.2013.03.005
    Boden, G. (2008). Obesity and free fatty acids. Endocrinol Metab Clin North Am, 37(3), 635-646, viii-ix. doi:10.1016/j.ecl.2008.06.007
    Boring, L., Gosling, J., Cleary, M., & Charo, I. F. (1998). Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature, 394(6696), 894-897. doi:10.1038/29788
    Bosetti, C., Rosato, V., Gallus, S., Cuzick, J., & La Vecchia, C. (2012). Aspirin and cancer risk: a quantitative review to 2011. Ann Oncol, 23(6), 1403-1415. doi: 10.1093/annonc/mds113
    Brady, N. J., Chuntova, P., & Schwertfeger, K. L. (2016). Macrophages: Regulators of the Inflammatory Microenvironment during Mammary Gland Development and Breast Cancer. Mediators Inflamm, 2016, 4549676. doi: 10.1155/2016/4549676
    Brakenhielm, E., Veitonmaki, N., Cao, R., Kihara, S., Matsuzawa, Y., Zhivotovsky, B., & Cao, Y. (2004). Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A, 101(8), 2476-2481.
    Brundu S, F. A. (2015). Polarization and Repolarization of Macrophages. Journal of Clinical and Cellular Immunology, 06(02). doi: 10.4172/2155-9899.1000319
    Bulun, S. E., Chen, D., Moy, I., Brooks, D. C., & Zhao, H. (2012). Aromatase, breast cancer and obesity: a complex interaction. Trends Endocrinol Metab, 23(2), 83-89. doi: 10.1016/j.tem.2011.10.003
    Byers, T., & Sedjo, R. L. (2015). Body fatness as a cause of cancer: epidemiologic clues to biologic mechanisms. Endocr Relat Cancer, 22(3), R125-134. doi: 10.1530/ERC-14-0580
    Calder, P. C., Ahluwalia, N., Albers, R., Bosco, N., Bourdet-Sicard, R., Haller, D., & Zhao, J. (2013). A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies. Br J Nutr, 109 Suppl 1, S1-34. doi: 10.1017/S0007114512005119
    Carroll, P. A., Healy, L., Lysaght, J., Boyle, T., Reynolds, J. V., Kennedy, M. J., & Connolly, E. M. (2011). Influence of the metabolic syndrome on leptin and leptin receptor in breast cancer. Mol Carcinog, 50(8), 643-651. doi: 10.1002/mc.20764
    Carter, J. C., & Church, F. C. (2009). Obesity and breast cancer: the roles of peroxisome proliferator-activated receptor-gamma and plasminogen activator inhibitor-1. PPAR Res, 2009, 345320. doi: 10.1155/2009/345320
    Castoldi, A., Naffah de Souza, C., Camara, N. O., & Moraes-Vieira, P. M. (2015). The Macrophage Switch in Obesity Development. Front Immunol, 6, 637. doi: 10.3389/fimmu.2015.00637
    Catalano, S., Marsico, S., Giordano, C., Mauro, L., Rizza, P., Panno, M. L., & Ando, S. (2003). Leptin enhances, via AP-1, expression of aromatase in the MCF-7 cell line. J Biol Chem, 278(31), 28668-28676. doi: 10.1074/jbc.M301695200
    Cawthorn, W. P., & Sethi, J. K. (2008). TNF-alpha and adipocyte biology. FEBS Lett, 582(1), 117-131. doi: 10.1016/j.febslet.2007.11.051
    Chait, A., & Kim, F. (2010). Saturated fatty acids and inflammation: who pays the toll? Arterioscler Thromb Vasc Biol, 30(4), 692-693. doi:10.1161/ATVBAHA.110.203984
    Chan, D. S., Vieira, A. R., Aune, D., Bandera, E. V., Greenwood, D. C., McTiernan, A., & Norat, T. (2014). Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol, 25(10), 1901-1914. doi: 10.1093/annonc/mdu042
    Chiu, H. H., Tsai, S. J., Tseng, Y. J., Wu, M. S., Liao, W. C., Huang, C. S., & Kuo, C. H. (2015). An efficient and robust fatty acid profiling method for plasma metabolomic studies by gas chromatography-mass spectrometry. Clin Chim Acta, 451(Pt B), 183-190. doi: 10.1016/j.cca.2015.09.028
    Chlebowski, R. T., Blackburn, G. L., Thomson, C. A., Nixon, D. W., Shapiro, A., Hoy, M. K., & Elashoff, R. M. (2006). Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study. J Natl Cancer Inst, 98(24), 1767-1776. doi: 10.1093/jnci/djj494
    Cleary, M. P., Grossmann, M. E., & Ray, A. (2010). Effect of obesity on breast cancer development. Vet Pathol, 47(2), 202-213. doi: 10.1177/0300985809357753
    Conti, I., & Rollins, B. J. (2004). CCL2 (monocyte chemoattractant protein-1) and cancer. Semin Cancer Biol, 14(3), 149-154. doi:10.1016/j.semcancer.2003.10.009
    Cullberg, K. B., Larsen, J. O., Pedersen, S. B., & Richelsen, B. (2014). Effects of LPS and dietary free fatty acids on MCP-1 in 3T3-L1 adipocytes and macrophages in vitro. Nutr Diabetes, 4, e113. doi:10.1038/nutd.2014.10
    Cuperlovic-Culf, M., Barnett, D. A., Culf, A. S., & Chute, I. (2010). Cell culture metabolomics: applications and future directions. Drug Discov Today, 15(15-16), 610-621. doi: 10.1016/j.drudis.2010.06.012
    Cuzick, J., Thorat, M. A., Bosetti, C., Brown, P. H., Burn, J., Cook, N. R., & Umar, A. (2015). Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol, 26(1), 47-57. doi: 10.1093/annonc/mdu225
    Dang, C. V. (2012). Links between metabolism and cancer. Genes Dev, 26(9), 877-890. doi:10.1101/gad.189365.112
    Dannenberg, A. J., Lippman, S. M., Mann, J. R., Subbaramaiah, K., & DuBois, R. N. (2005). Cyclooxygenase-2 and epidermal growth factor receptor: pharmacologic targets for chemoprevention. J Clin Oncol, 23(2), 254-266. doi: 10.1200/JCO.2005.09.112
    Davies, G. (2002). Cyclooxygenase-2 (COX-2), aromatase and breast cancer: a possible role for COX-2 inhibitors in breast cancer chemoprevention. Annals of Oncology, 13(5), 669-678. doi: 10.1093/annonc/mdf125
    Davis, J. E., Gabler Nk Fau - Walker-Daniels, J., Walker-Daniels J Fau - Spurlock, M. E., & Spurlock, M. E. The c-Jun N-terminal kinase mediates the induction of oxidative stress and insulin resistance by palmitate and toll-like receptor 2 and 4 ligands in 3T3-L1 adipocytes. (1439-4286 (Electronic))
    Davies, C., Pan, H., Godwin, J., Gray, R., Arriagada, R., Raina, V., & Peto, R. (2013). Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet, 381(9869), 805-816. doi:10.1016/s0140-6736(12)61963-1
    De Pergola, G., & Silvestris, F. (2013). Obesity as a major risk factor for cancer. J Obes, 2013, 291546. doi: 10.1155/2013/291546
    Deshmane, S. L., Kremlev, S., Amini, S., & Sawaya, B. E. (2009). Monocyte Chemoattractant Protein-1 (MCP-1): An Overview. J Interferon Cytokine Res, 29(6), 313-326. doi:10.1089/jir.2008.0027
    Diaby, V., Tawk, R., Sanogo, V., Xiao, H., & Montero, A. J. (2015). A review of systematic reviews of the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer. Breast Cancer Res Treat, 151(1), 27-40. doi:10.1007/s10549-015-3383-6
    Dieudonne, M. N., Bussiere, M., Dos Santos, E., Leneveu, M. C., Giudicelli, Y., & Pecquery, R. (2006). Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun, 345(1), 271-279. doi: 10.1016/j.bbrc.2006.04.076
    Dirat, B., Bochet, L., Dabek, M., Daviaud, D., Dauvillier, S., Majed, B., . . . Muller, C. (2011). Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res, 71(7), 2455-2465. doi: 10.1158/0008-5472.CAN-10-3323
    Dovizio, M., Bruno, A., Tacconelli, S., & Patrignani, P. (2013). Mode of action of aspirin as a chemopreventive agent. Recent Results Cancer Res, 191, 39-65. doi: 10.1007/978-3-642-30331-9_3
    Dowling, P., & Clynes, M. (2011). Conditioned media from cell lines: a complementary model to clinical specimens for the discovery of disease-specific biomarkers. Proteomics, 11(4), 794-804. doi: 10.1002/pmic.201000530
    Duan, Y., Chen, F., Zhang, A., Zhu, B., Sun, J., Xie, Q., & Chen, Z. (2014). Aspirin inhibits lipopolysaccharide-induced COX-2 expression and PGE2 production in porcine alveolar macrophages by modulating protein kinase C and protein tyrosine phosphatase activity. BMB Reports, 47(1), 45-50. doi:10.5483/BMBRep.2014.47.1.089
    Dunlap, S. M., Chiao, L. J., Nogueira, L., Usary, J., Perou, C. M., Varticovski, L., & Hursting, S. D. (2012). Dietary energy balance modulates epithelial-to-mesenchymal transition and tumor progression in murine claudin-low and basal-like mammary tumor models. Cancer Prev Res (Phila), 5(7), 930-942. doi: 10.1158/1940-6207.CAPR-12-0034
    Dunn, W. B., Bailey Nj Fau - Johnson, H. E., & Johnson, H. E. Measuring the metabolome: current analytical technologies. (0003-2654 (Print)).
    Eder, K., Baffy, N., Falus, A., & Fulop, A. K. (2009). The major inflammatory mediator interleukin-6 and obesity. Inflamm Res, 58(11), 727-736. doi:10.1007/s00011-009-0060-4
    Erreni, M., Mantovani, A., & Allavena, P. (2011). Tumor-associated Macrophages (TAM) and Inflammation in Colorectal Cancer. Cancer Microenviron, 4(2), 141-154. doi:10.1007/s12307-010-0052-5
    Esquivel-Velazquez, M., Ostoa-Saloma, P., Palacios-Arreola, M. I., Nava-Castro, K. E., Castro, J. I., & Morales-Montor, J. (2015). The role of cytokines in breast cancer development and progression. J Interferon Cytokine Res, 35(1), 1-16. doi:10.1089/jir.2014.0026
    Faggioni, R., Fantuzzi, G., Fuller, J., Dinarello, C. A., Feingold, K. R., & Grunfeld, C. (1998). IL-1 beta mediates leptin induction during inflammation. Am J Physiol, 274(1 Pt 2), R204-208.
    Feve, B., & Bastard, J. P. (2009). The role of interleukins in insulin resistance and type 2 diabetes mellitus. Nat Rev Endocrinol, 5(6), 305-311. doi:10.1038/nrendo.2009.62
    Fiehn, O. Metabolomics--the link between genotypes and phenotypes. (0167-4412 (Print)).
    Ford, N. A., Nunez, N. P., Holcomb, V. B., & Hursting, S. D. (2013). IGF1 dependence of dietary energy balance effects on murine Met1 mammary tumor progression, epithelial-to-mesenchymal transition, and chemokine expression. Endocr Relat Cancer, 20(1), 39-51. doi: 10.1530/ERC-12-0329
    Gabay, C. (2006). Interleukin-6 and chronic inflammation. Arthritis Res Ther, 8 Suppl 2, S3. doi:10.1186/ar1917
    Gan, L., Qiu, Z., Huang, J., Li, Y., Huang, H., Xiang, T., & Ren, G. (2016). Cyclooxygenase-2 in tumor-associated macrophages promotes metastatic potential of breast cancer cells through Akt pathway. Int J Biol Sci, 12(12), 1533-1543. doi:10.7150/ijbs.15943
    Garcia-Serrano, S., Moreno-Santos, I., Garrido-Sanchez, L., Gutierrez-Repiso, C., Garcia-Almeida, J. M., Garcia-Arnes, J., & Garcia-Fuentes, E. (2011). Stearoyl-CoA desaturase-1 is associated with insulin resistance in morbidly obese subjects. Mol Med, 17(3-4), 273-280. doi:10.2119/molmed.2010.00078
    Garcia-Tunon, I., Ricote, M., Ruiz, A., Fraile, B., Paniagua, R., & Royuela, M. (2005). IL-6, its receptors and its relationship with bcl-2 and bax proteins in infiltrating and in situ human breast carcinoma. Histopathology, 47(1), 82-89. doi:10.1111/j.1365-2559.2005.02178.x
    Gaudet, M. M., Press, M. F., Haile, R. W., Lynch, C. F., Glaser, S. L., Schildkraut, J., & Bernstein, J. L. (2011). Risk factors by molecular subtypes of breast cancer across a population-based study of women 56 years or younger. Breast Cancer Res Treat, 130(2), 587-597. doi: 10.1007/s10549-011-1616-x
    Ge, Y. L., Zhang, X., Zhang, J. Y., Hou, L., & Tian, R. H. (2009). The mechanisms on apoptosis by inhibiting VEGF expression in human breast cancer cells. Int Immunopharmacol, 9(4), 389-395. doi: 10.1016/j.intimp.2008.11.020
    Goers, L., Freemont, P., & Polizzi, K. M. (2014). Co-culture systems and technologies: taking synthetic biology to the next level. J R Soc Interface, 11(96). doi: 10.1098/rsif.2014.0065
    Gunter, M. J., Hoover, D. R., Yu, H., Wassertheil-Smoller, S., Rohan, T. E., Manson, J. E., & Strickler, H. D. (2009). Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst, 101(1), 48-60. doi: 10.1093/jnci/djn415
    Gu, L., Okada, Y., Clinton, S. K., Gerard, C., Sukhova, G. K., Libby, P., & Rollins, B. J. (1998). Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell, 2(2), 275-281.
    Guo, C., Buranych, A., Sarkar, D., Fisher, P. B., & Wang, X. Y. (2013). The role of tumor-associated macrophages in tumor vascularization. Vasc Cell, 5, 20. doi: 10.1186/2045-824x-5-20
    Guo, S., Liu, M., Wang, G., Torroella-Kouri, M., & Gonzalez-Perez, R. R. (2012). Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells. Biochim Biophys Acta, 1825(2), 207-222. doi: 10.1016/j.bbcan.2012.01.002
    Guo, Y., Xu, F., Lu, T., Duan, Z., & Zhang, Z. (2012). Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat Rev, 38(7), 904-910. doi:10.1016/j.ctrv.2012.04.007
    Gutierrez, L. S., Schulman, A., Brito-Robinson, T., Noria, F., Ploplis, V. A., & Castellino, F. J. (2000). Tumor development is retarded in mice lacking the gene for urokinase-type plasminogen activator or its inhibitor, plasminogen activator inhibitor-1. Cancer Res, 60(20), 5839-5847.
    Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646-674. doi: 10.1016/j.cell.2011.02.013
    Hankinson, S. E., Colditz, G. A., Hunter, D. J., Manson, J. E., Willett, W. C., Stampfer, M. J., & Speizer, F. E. (1995). Reproductive factors and family history of breast cancer in relation to plasma estrogen and prolactin levels in postmenopausal women in the Nurses' Health Study (United States). Cancer Causes Control, 6(3), 217-224.
    Hao, S., Liu, Y., Yu, K. D., Chen, S., Yang, W. T., & Shao, Z. M. (2015). Overweight as a Prognostic Factor for Triple-Negative Breast Cancers in Chinese Women. PLoS One, 10(6), e0129741. doi: 10.1371/journal.pone.0129741
    Harizi, H., Juzan, M., Pitard, V., Moreau, J. F., & Gualde, N. (2002). Cyclooxygenase-2-issued prostaglandin e(2) enhances the production of endogenous IL-10, which down-regulates dendritic cell functions. J Immunol, 168(5), 2255-2263.
    Harris, R. E., Beebe-Donk, J., & Alshafie, G. A. (2007). Cancer chemoprevention by cyclooxygenase 2 (COX-2) blockade: results of case control studies. Subcell Biochem, 42, 193-212.
    Hilvo, M., & Orešič, M. (2012). Regulation of lipid metabolism in breast cancer provides diagnostic and therapeutic opportunities. Clinical Lipidology, 7(2), 177-188. doi:10.2217/clp.12.10
    Hoeben, A., Landuyt, B., Highley, M. S., Wildiers, H., Van Oosterom, A. T., & De Bruijn, E. A. (2004). Vascular endothelial growth factor and angiogenesis. Pharmacol Rev, 56(4), 549-580. doi: 10.1124/pr.56.4.3
    Holmes, C. E., Jasielec, J., Levis, J. E., Skelly, J., & Muss, H. B. (2013). Initiation of aspirin therapy modulates angiogenic protein levels in women with breast cancer receiving tamoxifen therapy. Clin Transl Sci, 6(5), 386-390. doi: 10.1111/cts.12070
    Holmes, M. D., Chen, W. Y., Li, L., Hertzmark, E., Spiegelman, D., & Hankinson, S. E. (2010). Aspirin intake and survival after breast cancer. J Clin Oncol, 28(9), 1467-1472. doi: 10.1200/JCO.2009.22.7918
    Holt, D. J., Chamberlain, L. M., & Grainger, D. W. (2010). Cell-cell signaling in co-cultures of macrophages and fibroblasts. Biomaterials, 31(36), 9382-9394. doi: 10.1016/j.biomaterials.2010.07.101
    Hong, D. S., Angelo, L. S., & Kurzrock, R. (2007). Interleukin-6 and its receptor in cancer: implications for translational therapeutics. Cancer, 110(9), 1911-1928. doi:10.1002/cncr.22999
    Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993). Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science, 259(5091), 87-91.
    Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2008, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2008/, based on November 2010 SEER data submission, posted to the SEER web site, 2011.
    Hsieh, C. C., & Huang, Y. S. (2016). Aspirin Breaks the Crosstalk between 3T3-L1 Adipocytes and 4T1 Breast Cancer Cells by Regulating Cytokine Production. PLoS One, 11(1), e0147161. doi: 10.1371/journal.pone.0147161
    Huang, H., Park, C. K., Ryu, J. Y., Chang, E. J., Lee, Y., Kang, S. S., & Kim, H. H. (2006). Expression profiling of lipopolysaccharide target genes in RAW264.7 cells by oligonucleotide microarray analyses. Arch Pharm Res, 29(10), 890-897.
    Human Metabolome Database (HMDB). Available: http://www.hmdb.ca/
    Hundal, R. S., Petersen, K. F., Mayerson, A. B., Randhawa, P. S., Inzucchi, S., Shoelson, S. E., & Shulman, G. I. (2002). Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. Journal of Clinical Investigation, 109(10), 1321-1326. doi:10.1172/jci0214955
    Hunt, T. K., Aslam, R. S., Beckert, S., Wagner, S., Ghani, Q. P., Hussain, M. Z., & Sen, C. K. (2007). Aerobically derived lactate stimulates revascularization and tissue repair via redox mechanisms. Antioxid Redox Signal, 9(8), 1115-1124. doi:10.1089/ars.2007.1674
    Iikuni, N., Lam, Q. L., Lu, L., Matarese, G., & La Cava, A. (2008). Leptin and Inflammation. Curr Immunol Rev, 4(2), 70-79. doi: 10.2174/157339508784325046
    Ishikawa, H., Mutoh, M., Suzuki, S., Tokudome, S., Saida, Y., Abe, T., & Wakabayashi, K. (2014). The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomised trial. Gut, 63(11), 1755-1759. doi:10.1136/gutjnl-2013-305827
    Jacobo-Herrera, N. J., Perez-Plasencia, C., Camacho-Zavala, E., Gonzalez, G. F., Urrutia, E. L., Garcia-Castillo, V., & Zentella-Dehesa, A. (2014). Clinical evidence of the relationship between aspirin and breast cancer risk (review). Oncol Rep, 32(2), 451. doi:10.3892/or.2014.3270
    Jager, J., Gremeaux, T., Cormont, M., Le Marchand-Brustel, Y., & Tanti, J. F. (2007). Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology, 148(1), 241-251. doi:10.1210/en.2006-0692
    Jain, R., Strickler, H. D., Fine, E., & Sparano, J. A. (2013). Clinical studies examining the impact of obesity on breast cancer risk and prognosis. J Mammary Gland Biol Neoplasia, 18(3-4), 257-266. doi:10.1007/s10911-013-9307-3
    Jin, H., Tu, D., Zhao, N., Shepherd, L. E., & Goss, P. E. (2012). Longer-term outcomes of letrozole versus placebo after 5 years of tamoxifen in the NCIC CTG MA.17 trial: analyses adjusting for treatment crossover. J Clin Oncol, 30(7), 718-721. doi:10.1200/jco.2010.34.4010
    Jung, U. J., & Choi, M. S. (2014). Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci, 15(4), 6184-6223. doi: 10.3390/ijms15046184
    Kajdaniuk, D., Marek, B., Borgiel-Marek, H., & Kos-Kudla, B. (2013). Transforming growth factor beta1 (TGFbeta1) in physiology and pathology. Endokrynol Pol, 64(5), 384-396. doi:10.5603/ep.2013.0022
    Kamei, N., Tobe, K., Suzuki, R., Ohsugi, M., Watanabe, T., Kubota, N., . . . Kadowaki, T. (2006). Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem, 281(36), 26602-26614. doi:10.1074/jbc.M601284200
    Kanda, H., Tateya, S., Tamori, Y., Kotani, K., Hiasa, K., Kitazawa, R., . . . Kasuga, M. (2006). MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest, 116(6), 1494-1505. doi:10.1172/jci26498
    Kato, Y., Ozawa, S., Tsukuda, M., Kubota, E., Miyazaki, K., St-Pierre, Y., & Hata, R. (2007). Acidic extracellular pH increases calcium influx-triggered phospholipase D activity along with acidic sphingomyelinase activation to induce matrix metalloproteinase-9 expression in mouse metastatic melanoma. FEBS J, 274(12), 3171-3183. doi:10.1111/j.1742-4658.2007.05848.x
    Kaur P Fau - Kaur, P., Nagaraja Gm Fau - Nagaraja, G. M., Zheng H Fau - Zheng, H., Gizachew D Fau - Gizachew, D., Galukande M Fau - Galukande, M., Krishnan S Fau - Krishnan, S., & Asea A Fau - Asea, A. A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs) exhibits similar aggressive phenotype to the human disease. (1471-2407 (Electronic))
    KEGG PATHWAY Database. Available: http://www.genome.jp/kegg/pathway.html
    Kern, P. A., Ranganathan, S., Li, C., Wood, L., & Ranganathan, G. (2001). Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab, 280(5), E745-751.
    Khan, S., Shukla, S., Sinha, S., & Meeran, S. M. (2013). Role of adipokines and cytokines in obesity-associated breast cancer: therapeutic targets. Cytokine Growth Factor Rev, 24(6), 503-513. doi: 10.1016/j.cytogfr.2013.10.001
    Khandekar, M. J., Cohen, P., & Spiegelman, B. M. (2011). Molecular mechanisms of cancer development in obesity. Nat Rev Cancer, 11(12), 886-895
    Kim, E. J., Choi, M. R., Park, H., Kim, M., Hong, J. E., Lee, J. Y., & Yoon Park, J. H. (2011). Dietary fat increases solid tumor growth and metastasis of 4T1 murine mammary carcinoma cells and mortality in obesity-resistant BALB/c mice. Breast Cancer Res, 13(4), R78. doi: 10.1186/bcr2927
    Kim, H. H., & Park, C. S. (2003). Methionine cytotoxicity in the human breast cancer cell line MCF-7. In Vitro Cell Dev Biol Anim, 39(3-4), 117-119. doi: 10.1007/s11626-003-0004-1
    Kim, K. J., Li, B., Winer, J., Armanini, M., Gillett, N., Phillips, H. S., & Ferrara, N. (1993). Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature, 362(6423), 841-844. doi: 10.1038/362841a0
    Kim, S., Shore, D. L., Wilson, L. E., Sanniez, E. I., Kim, J. H., Taylor, J. A., & Sandler, D. P. (2015). Lifetime use of nonsteroidal anti-inflammatory drugs and breast cancer risk: results from a prospective study of women with a sister with breast cancer. BMC Cancer, 15(1), 960. doi: 10.1186/s12885-015-1979-1
    Knoop, A., Andreasen, P. A., Andersen, J. A., Hansen, S., Laenkholm, A. V., Simonsen, A. C., & Rose, C. (1998). Prognostic significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in primary breast cancer. Br J Cancer, 77(6), 932-940.
    Korniluk, A., Koper, O., Kemona, H., & Dymicka-Piekarska, V. (2016). From inflammation to cancer. Ir J Med Sci. doi: 10.1007/s11845-016-1464-0
    Kune, G. A., Kune, S., & Watson, L. F. (1988). Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res, 48(15), 4399-4404
    López-Lázaro, M. Understanding why aspirin prevents cancer and why consuming very hot beverages and foods increases esophageal cancer risk. Controlling the division rates of stem cells is an important strategy to prevent cancer: Oncoscience. 2015;2(10):849-56.
    Lai, Y. S., Chen, W. C., Kuo, T. C., Ho, C. T., Kuo, C. H., Tseng, Y. J., & Sheen, L. Y. (2015). Mass-Spectrometry-Based Serum Metabolomics of a C57BL/6J Mouse Model of High-Fat-Diet-Induced Non-alcoholic Fatty Liver Disease Development. J Agric Food Chem, 63(35), 7873-7884. doi: 10.1021/acs.jafc.5b02830
    Landskron, G., De la Fuente, M., Thuwajit, P., Thuwajit, C., & Hermoso, M. A. (2014). Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res, 2014, 149185. doi:10.1155/2014/149185
    Lee, C., Raffaghello, L., Brandhorst, S., Safdie, F. M., Bianchi, G., Martin-Montalvo, A., & Longo, V. D. (2012). Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med, 4(124), 124ra127. doi: 10.1126/scitranslmed.3003293
    Lenzen, S., Formanek, H., & Panten, U. (1982). Signal function of metabolism of neutral amino acids and 2-keto acids for initiation of insulin secretion. J Biol Chem, 257(12), 6631-6633.
    Levchuk, A. A., Faron, R. A., Khrustalev, S. A., & Raushenbakh, M. O. (1986). [Effect of the carcinogenic tyrosine metabolite p-hydroxyphenyllactic acid on the ascorbic acid concentration in the organs and blood of mice]. Biull Eksp Biol Med, 102(10), 462-463.
    Li, H., Yang, B., Huang, J., Lin, Y., Xiang, T., Wan, J., & Ren, G. (2015). Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive-feedback loop between macrophages and cancer cells. Oncotarget, 6(30), 29637-29650. doi: 10.18632/oncotarget.4936
    Li, N., Qin, J., Lan, L., Zhang, H., Liu, F., Wu, Z., & Wang, Y. (2015). PTEN inhibits macrophage polarization from M1 to M2 through CCL2 and VEGF-A reduction and NHERF-1 synergism. Cancer Biol Ther, 16(2), 297-306. doi:10.1080/15384047.2014.1002353
    Liu, B., Qu, L., & Yan, S. (2015). Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity. Cancer Cell Int, 15, 106. doi: 10.1186/s12935-015-0260-7
    Liu, J., Zhang, N., Li, Q., Zhang, W., Ke, F., Leng, Q., & Wang, H. (2011). Tumor-associated macrophages recruit CCR6+ regulatory T cells and promote the development of colorectal cancer via enhancing CCL20 production in mice. PLoS One, 6(4), e19495. doi: 10.1371/journal.pone.0019495
    Liu, J., Liao, S., Diop-Frimpong, B., Chen, W., Goel, S., Naxerova, K., & Xu, L. (2012). TGF-beta blockade improves the distribution and efficacy of therapeutics in breast carcinoma by normalizing the tumor stroma. Proc Natl Acad Sci U S A, 109(41), 16618-16623. doi:10.1073/pnas.1117610109
    Liu, Q., Li, Y., Niu, Z., Zong, Y., Wang, M., Yao, L., & Zhao, Y. (2016). Atorvastatin (Lipitor) attenuates the effects of aspirin on pancreatic cancerogenesis and the chemotherapeutic efficacy of gemcitabine on pancreatic cancer by promoting M2 polarized tumor associated macrophages. J Exp Clin Cancer Res, 35, 33. doi:10.1186/s13046-016-0304-4
    Louie, S. M., Roberts, L. S., & Nomura, D. K. (2013). Mechanisms linking obesity and cancer. Biochim Biophys Acta, 1831(10), 1499-1508. doi: 10.1016/j.bbalip.2013.02.008
    Makki, K., Froguel, P., & Wolowczuk, I. (2013). Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm, 2013, 139239. doi:10.1155/2013/139239
    Malekshah, A. K., Moghaddam, A. E., & Daraka, S. M. (2006). Comparison of conditioned medium and direct co-culture of human granulosa cells on mouse embryo development. Indian J Exp Biol, 44(3), 189-192.
    Mantovani, A., Schioppa, T., Porta, C., Allavena, P., & Sica, A. (2006). Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev, 25(3), 315-322. doi:10.1007/s10555-006-9001-7
    Mantovani, A., Biswas, S. K., Galdiero, M. R., Sica, A., & Locati, M. (2013). Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol, 229(2), 176-185. doi: 10.1002/path.4133
    Martinez, F. O., & Gordon, S. (2014). The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep, 6, 13. doi: 10.12703/P6-13
    Mazid, M. A., Chowdhury, A. A., Nagao, K., Nishimura, K., Jisaka, M., Nagaya, T., & Yokota, K. (2006). Endogenous 15-deoxy-Delta(12,14)-prostaglandin J(2) synthesized by adipocytes during maturation phase contributes to upregulation of fat storage. FEBS Lett, 580(30), 6885-6890. doi: 10.1016/j.febslet.2006.11.049
    Maughan, K. L., Lutterbie, M. A., & Ham, P. S. (2010). Treatment of breast cancer. Am Fam Physician, 81(11), 1339-1346.
    McQuaid, K. R., & Laine, L. (2006). Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med, 119(8), 624-638. doi: 10.1016/j.amjmed.2005.10.039
    McTiernan, A., Rajan, K. B., Tworoger, S. S., Irwin, M., Bernstein, L., Baumgartner, R., & Ballard-Barbash, R. (2003). Adiposity and sex hormones in postmenopausal breast cancer survivors. J Clin Oncol, 21(10), 1961-1966. doi: 10.1200/JCO.2003.07.057
    Medrek, C., Ponten, F., Jirstrom, K., & Leandersson, K. (2012). The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients. BMC Cancer, 12, 306. doi: 10.1186/1471-2407-12-306
    Menge, B. A., Schrader, H., Ritter, P. R., Ellrichmann, M., Uhl, W., Schmidt, W. E., & Meier, J. J. (2010). Selective amino acid deficiency in patients with impaired glucose tolerance and type 2 diabetes. Regul Pept, 160(1-3), 75-80. doi: 10.1016/j.regpep.2009.08.001
    Millikan, R. C., Newman, B., Tse, C. K., Moorman, P. G., Conway, K., Dressler, L. G., & Perou, C. M. (2008). Epidemiology of basal-like breast cancer. Breast Cancer Res Treat, 109(1), 123-139. doi: 10.1007/s10549-007-9632-6
    Moses, H., & Barcellos-Hoff, M. H. (2011). TGF-beta biology in mammary development and breast cancer. Cold Spring Harb Perspect Biol, 3(1), a003277. doi:10.1101/cshperspect.a003277
    Monirujjaman, M., & Ferdouse, A. (2014). Metabolic and Physiological Roles of Branched-Chain Amino Acids. Advances in Molecular Biology, 2014, 1-6. doi: 10.1155/2014/364976
    Mougiakakos, D., Johansson, C. C., Trocme, E., All-Ericsson, C., Economou, M. A., Larsson, O., & Kiessling, R. (2010). Intratumoral forkhead box P3-positive regulatory T cells predict poor survival in cyclooxygenase-2-positive uveal melanoma. Cancer, 116(9), 2224-2233. doi: 10.1002/cncr.24999
    Muller-Quernheim, U. C., Potthast, L., Muller-Quernheim, J., & Zissel, G. (2012). Tumor-cell co-culture induced alternative activation of macrophages is modulated by interferons in vitro. J Interferon Cytokine Res, 32(4), 169-177. doi:10.1089/jir.2011.0020
    Muting, D., Wuzel, H., Bucsis, L., & Flasshoff, H.-J. Urinary p-hydroxyphenyllactic acid as indicator of hepatic encephalopathy in patients with hepatic cirrhosis. The Lancet, 326(8468), 1365-1366. doi: 10.1016/S0140-6736(85)92662-5
    Na, Y. R., Yoon, Y. N., Son, D., Jung, D., Gu, G. J., & Seok, S. H. (2015). Consistent inhibition of cyclooxygenase drives macrophages towards the inflammatory phenotype. PLoS One, 10(2), e0118203. doi: 10.1371/journal.pone.0118203
    Na, Y. R., Yoon, Y. N., Son, D. I., & Seok, S. H. (2013). Cyclooxygenase-2 inhibition blocks M2 macrophage differentiation and suppresses metastasis in murine breast cancer model. PLoS One, 8(5), e63451. doi: 10.1371/journal.pone.0063451
    Nakanishi, Y., Nakatsuji, M., Seno, H., Ishizu, S., Akitake-Kawano, R., Kanda, K., & Chiba, T. (2011). COX-2 inhibition alters the phenotype of tumor-associated macrophages from M2 to M1 in ApcMin/+ mouse polyps. Carcinogenesis, 32(9), 1333-1339. doi: 10.1093/carcin/bgr128
    Neels, J. G., & Olefsky, J. M. (2006). Inflamed fat: what starts the fire? J Clin Invest, 116(1), 33-35. doi: 10.1172/jci27280
    Newgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., & Svetkey, L. P. (2009). A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab, 9(4), 311-326. doi: 10.1016/j.cmet.2009.02.002
    Nishida, N., Yano, H., Nishida, T., Kamura, T., & Kojiro, M. (2006). Angiogenesis in Cancer. Vasc Health Risk Manag, 2(3), 213-219.
    Ntambi, J. M., & Young-Cheul, K. (2000). Adipocyte differentiation and gene expression. J Nutr, 130(12), 3122s-3126s.
    Odegaard, J. I., Ricardo-Gonzalez, R. R., Goforth, M. H., Morel, C. R., Subramanian, V., Mukundan, L., & Chawla, A. (2007). Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature, 447(7148), 1116-1120. doi: 10.1038/nature05894
    Ogawa, F., Amano, H., Ito, Y., Matsui, Y., Hosono, K., Kitasato, H., & Majima, M. (2014). Aspirin reduces lung cancer metastasis to regional lymph nodes. Biomed Pharmacother, 68(1), 79-86. doi: 10.1016/j.biopha.2013.11.006
    Ogston, N. C., Karastergiou, K., Hosseinzadeh-Attar, M. J., Bhome, R., Madani, R., Stables, M., & Mohamed-Ali, V. (2008). Low-dose acetylsalicylic acid inhibits the secretion of interleukin-6 from white adipose tissue. Int J Obes (Lond), 32(12), 1807-1815. doi: 10.1038/ijo.2008.190
    Ohta, M., Kitadai, Y., Tanaka, S., Yoshihara, M., Yasui, W., Mukaida, N., & Chayama, K. (2003). Monocyte chemoattractant protein-1 expression correlates with macrophage infiltration and tumor vascularity in human gastric carcinomas. Int J Oncol, 22(4), 773-778
    Pan, Z., & Raftery, D. (2007). Comparing and combining NMR spectroscopy and mass spectrometry in metabolomics. Anal Bioanal Chem, 387(2), 525-527. doi: 10.1007/s00216-006-0687-8
    Park, M. Y., & Sung, M. K. (2015). Carnosic Acid Inhibits Lipid Accumulation in 3T3-L1 Adipocytes Through Attenuation of Fatty Acid Desaturation. J Cancer Prev, 20(1), 41-49. doi:10.15430/JCP.2015.20.1.41
    Pierobon, M., & Frankenfeld, C. L. (2013). Obesity as a risk factor for triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat, 137(1), 307-314. doi: 10.1007/s10549-012-2339-3
    Protani, M., Coory, M., & Martin, J. H. (2010). Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat, 123(3), 627-635. doi: 10.1007/s10549-010-0990-0
    Pucci, F., Venneri, M. A., Biziato, D., Nonis, A., Moi, D., Sica, A., & De Palma, M. (2009). A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood "resident" monocytes, and embryonic macrophages suggests common functions and developmental relationships. Blood, 114(4), 901-914. doi: 10.1182/blood-2009-01-200931
    Quail, D. F., & Joyce, J. A. (2013). Microenvironmental regulation of tumor progression and metastasis. Nat Med, 19(11), 1423-1437. doi: 10.1038/nm.3394
    Ramos-Nino, M. E. (2013). The role of chronic inflammation in obesity-associated cancers. ISRN Oncol, 2013, 697521. doi:10.1155/2013/697521
    Ren, K., & Torres, R. (2009). Role of interleukin-1beta during pain and inflammation. Brain Res Rev, 60(1), 57-64. doi:10.1016/j.brainresrev.2008.12.020
    Rochfort, S. Metabolomics reviewed: a new "omics" platform technology for systems biology and implications for natural products research. (0163-3864 (Print)).
    Rogers, T. L., & Holen, I. (2011). Tumour macrophages as potential targets of bisphosphonates. J Transl Med, 9, 177. doi: 10.1186/1479-5876-9-177
    Romero-Garcia, S., Moreno-Altamirano, M. M., Prado-Garcia, H., & Sanchez-Garcia, F. J. (2016). Lactate Contribution to the Tumor Microenvironment: Mechanisms, Effects on Immune Cells and Therapeutic Relevance. Front Immunol, 7, 52. doi:10.3389/fimmu.2016.00052
    Rose, D. P., & Vona-Davis, L. (2010). Interaction between menopausal status and obesity in affecting breast cancer risk. Maturitas, 66(1), 33-38. doi: 10.1016/j.maturitas.2010.01.019
    Roszer, T. (2015). Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms. Mediators Inflamm, 2015, 816460. doi: 10.1155/2015/816460
    Rotter, V., Nagaev, I., & Smith, U. (2003). Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem, 278(46), 45777-45784. doi:10.1074/jbc.M301977200
    Ruffell, B., Chang-Strachan, D., Chan, V., Rosenbusch, A., Ho, C. M., Pryer, N., & Coussens, L. M. (2014). Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell, 26(5), 623-637. doi: 10.1016/j.ccell.2014.09.006
    Ryan, D., & Robards, K. Metabolomics: The greatest omics of them all? (0003-2700 (Print)).
    Sartipy, P., & Loskutoff, D. J. (2003). Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci U S A, 100(12), 7265-7270. doi:10.1073/pnas.1133870100
    Saxena, R. K., Vallyathan, V., & Lewis, D. M. (2003). Evidence for lipopolysaccharide-induced differentiation of RAW264.7 murine macrophage cell line into dendritic like cells. J Biosci, 28(1), 129-134.
    Scheller, J., Chalaris, A., Schmidt-Arras, D., & Rose-John, S. (2011). The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta, 1813(5), 878-888. doi:10.1016/j.bbamcr.2011.01.034
    Scott, L., Lamb, J., Smith, S., & Wheatley, D. N. (2000). Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells. Br J Cancer, 83(6), 800-810. doi:10.1054/bjoc.2000.1353
    Shackelford, R. E., Alford, P. B., Xue, Y., Thai, S. F., Adams, D. O., & Pizzo, S. (1997). Aspirin inhibits tumor necrosis factoralpha gene expression in murine tissue macrophages. Mol Pharmacol, 52(3), 421-429
    Shi, C., Zhang, N., Feng, Y., Cao, J., Chen, X., & Liu, B. (2017). Aspirin Inhibits IKK-beta-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator. Cell Physiol Biochem, 41(4), 1313-1324. doi:10.1159/000464434
    Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006). TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest, 116(11), 3015-3025. doi: 10.1172/JCI28898
    Sica, A., Allavena, P., & Mantovani, A. (2008). Cancer related inflammation: the macrophage connection. Cancer Lett, 267(2), 204-215. doi: 10.1016/j.canlet.2008.03.028
    Sica, A., Erreni, M., Allavena, P., & Porta, C. (2015). Macrophage polarization in pathology. Cell Mol Life Sci, 72(21), 4111-4126. doi: 10.1007/s00018-015-1995-y
    Singletary, S. E. (2003). Rating the Risk Factors for Breast Cancer. Ann Surg, 237(4), 474-482. doi: 10.1097/01.sla.0000059969.64262.87
    Sjogren, P., Sierra-Johnson, J., Gertow, K., Rosell, M., Vessby, B., de Faire, U., & Fisher, R. M. (2008). Fatty acid desaturases in human adipose tissue: relationships between gene expression, desaturation indexes and insulin resistance. Diabetologia, 51(2), 328-335. doi:10.1007/s00125-007-0876-9
    Sjostrom, L., Narbro, K., Sjostrom, C. D., Karason, K., Larsson, B., Wedel, H., & Carlsson, L. M. (2007). Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med, 357(8), 741-752. doi: 10.1056/NEJMoa066254
    Slamon, D. J., Godolphin, W., Jones, L. A., Holt, J. A., Wong, S. G., & Keith, D. E. (1989). Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science, 244(4905), 707-712
    Smith, I., Procter, M., Gelber, R. D., Guillaume, S., Feyereislova, A., Dowsett, M., & Piccart-Gebhart, M. J. (2007). 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet, 369(9555), 29-36. doi:10.1016/s0140-6736(07)60028-2
    Solanky, K. S., Bailey, N. J. C., Beckwith-Hall, B. M., Davis, A., Bingham, S., Holmes, E., & Cassidy, A. (2003). Application of biofluid 1H nuclear magnetic resonance-based metabonomic techniques for the analysis of the biochemical effects of dietary isoflavones on human plasma profile. Analytical Biochemistry, 323(2), 197-204. doi: 10.1016/j.ab.2003.08.028
    Solinas, G., Germano, G., Mantovani, A., & Allavena, P. (2009). Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol, 86(5), 1065-1073. doi: 10.1189/jlb.0609385
    Song, H., Jung, J. I., Cho, H. J., Her, S., Kwon, S. H., Yu, R., & Park, J. H. (2015). Inhibition of tumor progression by oral piceatannol in mouse 4T1 mammary cancer is associated with decreased angiogenesis and macrophage infiltration. J Nutr Biochem, 26(11), 1368-1378. doi:10.1016/j.jnutbio.2015.07.005
    Sousa, S., Brion, R., Lintunen, M., Kronqvist, P., Sandholm, J., Monkkonen, J., & Maatta, J. A. (2015). Human breast cancer cells educate macrophages toward the M2 activation status. Breast Cancer Res, 17, 101. doi: 10.1186/s13058-015-0621-0
    Speaker, K. J., & Fleshner, M. (2012). Interleukin-1 beta: a potential link between stress and the development of visceral obesity. BMC Physiol, 12, 8. doi:10.1186/1472-6793-12-8
    Spratlin, J. L., Serkova, N. J., & Eckhardt, S. G. (2009). Clinical applications of metabolomics in oncology: a review. Clin Cancer Res, 15(2), 431-440. doi: 10.1158/1078-0432.CCR-08-1059
    Su, Y. F., Yang, S. H., Lee, Y. H., Wu, B. C., Huang, S. C., Liu, C. M., & Yang, H. W. (2014). Aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of pentose phosphate pathway. Eur J Pharmacol, 738, 101-110. doi:10.1016/j.ejphar.2014.03.009
    Subbegowda, R., & Frommel, T. O. (1998). Aspirin toxicity for human colonic tumor cells results from necrosis and is accompanied by cell cycle arrest. Cancer Res, 58(13), 2772-2776.
    Sung, H. K., Doh, K. O., Son, J. E., Park, J. G., Bae, Y., Choi, S., & Nagy, A. (2013). Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis. Cell Metab, 17(1), 61-72. doi: 10.1016/j.cmet.2012.12.010
    Sugimoto, M., Sakagami, H., Yokote, Y., Onuma, H., Kaneko, M., Mori, M., & Tomita, M. (2011). Non-targeted metabolite profiling in activated macrophage secretion. Metabolomics, 8(4), 624-633. doi:10.1007/s11306-011-0353-9
    Sullivan, N. J., Sasser, A. K., Axel, A. E., Vesuna, F., Raman, V., Ramirez, N., & Hall, B. M. (2009). Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells. Oncogene, 28(33), 2940-2947. doi:10.1038/onc.2009.180
    Takahashi, K., Mizuarai, S., Araki, H., Mashiko, S., Ishihara, A., Kanatani, A., & Kotani, H. (2003). Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice. J Biol Chem, 278(47), 46654-46660. doi:10.1074/jbc.M309895200
    Tan, A. R., Alexe, G., & Reiss, M. (2009). Transforming growth factor-beta signaling: emerging stem cell target in metastatic breast cancer? Breast Cancer Res Treat, 115(3), 453-495. doi:10.1007/s10549-008-0184-1
    Tanaka, S., Tatsuguchi, A., Futagami, S., Gudis, K., Wada, K., Seo, T., & Sakamoto, C. (2006). Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma. Gut, 55(1), 54-61. doi:10.1136/gut.2004.059824
    Tang, C. H., Lu, D. Y., Yang, R. S., Tsai, H. Y., Kao, M. C., Fu, W. M., & Chen, Y. F. (2007). Leptin-Induced IL-6 Production Is Mediated by Leptin Receptor, Insulin Receptor Substrate-1, Phosphatidylinositol 3-Kinase, Akt, NF- B, and p300 Pathway in Microglia. The Journal of Immunology, 179(2), 1292-1302. doi: 10.4049/jimmunol.179.2.1292
    Tao, Z., Shi, A., Lu, C., Song, T., Zhang, Z., & Zhao, J. (2015). Breast Cancer: Epidemiology and Etiology. Cell Biochem Biophys, 72(2), 333-338. doi: 10.1007/s12013-014-0459-6
    Terakura, D., Shimizu, M., Iwasa, J., Baba, A., Kochi, T., Ohno, T., & Moriwaki, H. (2012). Preventive effects of branched-chain amino acid supplementation on the spontaneous development of hepatic preneoplastic lesions in C57BL/KsJ-db/db obese mice. Carcinogenesis, 33(12), 2499-2506. doi: 10.1093/carcin/bgs303
    Thorat, M. A., & Cuzick, J. (2013). Role of aspirin in cancer prevention. Curr Oncol Rep, 15(6), 533-540. doi: 10.1007/s11912-013-0351-3
    Tretli, S. (1989). Height and weight in relation to breast cancer morbidity and mortality. A prospective study of 570,000 women in Norway. Int J Cancer, 44(1), 23-30.
    Tworoger, S. S., Eliassen, A. H., Kelesidis, T., Colditz, G. A., Willett, W. C., Mantzoros, C. S., & Hankinson, S. E. (2007). Plasma adiponectin concentrations and risk of incident breast cancer. J Clin Endocrinol Metab, 92(4), 1510-1516. doi: 10.1210/jc.2006-1975
    Tymoszuk, P., Evens, H., Marzola, V., Wachowicz, K., Wasmer, M. H., Datta, S., & Doppler, W. (2014). In situ proliferation contributes to accumulation of tumor-associated macrophages in spontaneous mammary tumors. Eur J Immunol, 44(8), 2247-2262. doi: 10.1002/eji.201344304
    Usman, M. W., Luo, F., Cheng, H., Zhao, J. J., & Liu, P. (2015). Chemopreventive effects of aspirin at a glance. Biochim Biophys Acta, 1855(2), 254-263. doi: 10.1016/j.bbcan.2015.03.007
    Valkovic, T., Dobrila, F., Melato, M., Sasso, F., Rizzardi, C., & Jonjic, N. (2002). Correlation between vascular endothelial growth factor, angiogenesis, and tumor-associated macrophages in invasive ductal breast carcinoma. Virchows Arch, 440(6), 583-588. doi: 10.1007/s004280100458
    van Kruijsdijk, R. C., van der Wall, E., & Visseren, F. L. (2009). Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomarkers Prev, 18(10), 2569-2578. doi: 10.1158/1055-9965.epi-09-0372
    Verma, R., Bowen, R. L., Slater, S. E., Mihaimeed, F., & Jones, J. L. (2012). Pathological and epidemiological factors associated with advanced stage at diagnosis of breast cancer. British Medical Bulletin, 103(1), 129-145. doi: 10.1093/bmb/lds018
    Vinknes, K. J., Elshorbagy, A. K., Drevon, C. A., Nurk, E., Tell, G. S., Nygard, O., & Refsum, H. (2013). Associations between plasma polyunsaturated fatty acids, plasma stearoyl-CoA desaturase indices and body fat. Obesity (Silver Spring), 21(9), E512-519. doi:10.1002/oby.20457
    Vona-Davis, L., & Rose, D. P. (2007). Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer, 14(2), 189-206. doi: 10.1677/ERC-06-0068
    Wang, C., Gao, C., Meng, K., Qiao, H., & Wang, Y. (2015). Human adipocytes stimulate invasion of breast cancer MCF-7 cells by secreting IGFBP-2. PLoS One, 10(3), e0119348. doi:10.1371/journal.pone.0119348
    Wang, L., Xu, M. L., Liu, J., Wang, Y., Hu, J. H., & Wang, M. H. (2015). Sonchus asper extract inhibits LPS-induced oxidative stress and pro-inflammatory cytokine production in RAW264.7 macrophages. Nutr Res Pract, 9(6), 579-585. doi: 10.4162/nrp.2015.9.6.579
    Wang, Q., Ni, H., Lan, L., Wei, X., Xiang, R., & Wang, Y. (2010). Fra-1 protooncogene regulates IL-6 expression in macrophages and promotes the generation of M2d macrophages. Cell Res, 20(6), 701-712. doi: 10.1038/cr.2010.52
    Wang, Z., Lee, Y., Eun, J. S., & Bae, E. J. (2014). Inhibition of adipocyte inflammation and macrophage chemotaxis by butein. Eur J Pharmacol, 738, 40-48. doi: 10.1016/j.ejphar.2014.05.031
    Want, E. J., O'Maille G Fau - Smith, C. A., Smith Ca Fau - Brandon, T. R., Brandon Tr Fau - Uritboonthai, W., Uritboonthai W Fau - Qin, C., Qin C Fau - Trauger, S. A., & Siuzdak, G. Solvent-dependent metabolite distribution, clustering, and protein extraction for serum profiling with mass spectrometry. (0003-2700 (Print))
    Weber, A., Wasiliew, P., & Kracht, M. (2010). Interleukin-1 (IL-1) pathway. Sci Signal, 3(105), cm1. doi:10.1126/scisignal.3105cm1
    Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W., Jr. (2003). Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest, 112(12), 1796-1808. doi:10.1172/jci19246
    Weisberg, S. P., Hunter, D., Huber, R., Lemieux, J., Slaymaker, S., Vaddi, K., & Ferrante, A. W., Jr. (2006). CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest, 116(1), 115-124. doi: 10.1172/jci24335
    WHO Media Center, Geneva, 2015. Obesity and overweight. Facts about overweight and obesity.
    Williams, C. B., Yeh, E. S., & Soloff, A. C. (2016). Tumor-associated macrophages: unwitting accomplices in breast cancer malignancy. NPJ Breast Cancer, 2. doi: 10.1038/npjbcancer.2015.25
    Wu, V. S., Kanaya, N., Lo, C., Mortimer, J., & Chen, S. (2015). From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer? J Steroid Biochem Mol Biol, 153, 45-53. doi:10.1016/j.jsbmb.2015.05.005
    Wu, Y., & Zhou, B. P. (2010). TNF-alpha/NF-kappaB/Snail pathway in cancer cell migration and invasion. Br J Cancer, 102(4), 639-644. doi:10.1038/sj.bjc.6605530
    Xia, J., Sinelnikov, I. V., Han, B., & Wishart, D. S. (2015). MetaboAnalyst 3.0--making metabolomics more meaningful. Nucleic Acids Res, 43(W1), W251-257. doi: 10.1093/nar/gkv380
    Xie, H., Hanai, J., Ren, J. G., Kats, L., Burgess, K., Bhargava, P., & Seth, P. (2014). Targeting lactate dehydrogenase--a inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor-initiating cells. Cell Metab, 19(5), 795-809. doi:10.1016/j.cmet.2014.03.003
    Yang, J., Liao, D., Chen, C., Liu, Y., Chuang, T. H., Xiang, R., & Luo, Y. (2013). Tumor-associated macrophages regulate murine breast cancer stem cells through a novel paracrine EGFR/Stat3/Sox-2 signaling pathway. Stem Cells, 31(2), 248-258. doi: 10.1002/stem.1281
    Yang, Y., Qin, J., Lan, L., Li, N., Wang, C., He, P., & Wang, Y. (2014). M-CSF cooperating with NFkappaB induces macrophage transformation from M1 to M2 by upregulating c-Jun. Cancer Biol Ther, 15(1), 99-107. doi:10.4161/cbt.26718
    Yeop Han, C., Kargi, A. Y., Omer, M., Chan, C. K., Wabitsch, M., O'Brien, K. D., & Chait, A. (2010). Differential effect of saturated and unsaturated free fatty acids on the generation of monocyte adhesion and chemotactic factors by adipocytes: dissociation of adipocyte hypertrophy from inflammation. Diabetes, 59(2), 386-396. doi:10.2337/db09-0925
    Yin, M. J., Yamamoto, Y., & Gaynor, R. B. (1998). The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature, 396(6706), 77-80. doi:10.1038/23948
    Yoshida, S., Amano, H., Hayashi, I., Kitasato, H., Kamata, M., Inukai, M., & Majima, M. (2003). COX-2/VEGF-Dependent Facilitation of Tumor-Associated Angiogenesis and Tumor Growth in vivo. Laboratory Investigation, 83(10), 1385-1394. doi:10.1097/01.lab.0000090159.53224.b9
    Youlden, D. R., Cramb, S. M., Dunn, N. A., Muller, J. M., Pyke, C. M., & Baade, P. D. (2012). The descriptive epidemiology of female breast cancer: an international comparison of screening, incidence, survival and mortality. Cancer Epidemiol, 36(3), 237-248. doi: 10.1016/j.canep.2012.02.007
    Yuan, A., Hsiao, Y. J., Chen, H. Y., Chen, H. W., Ho, C. C., Chen, Y. Y., & Yang, P. C. (2015). Opposite Effects of M1 and M2 Macrophage Subtypes on Lung Cancer Progression. Sci Rep, 5, 14273. doi:10.1038/srep14273
    Yung, R. L., & Ligibel, J. A. (2016). Obesity and breast cancer: risk, outcomes, and future considerations. Clin Adv Hematol Oncol, 14(10), 790-797.
    Zahorska-Markiewicz, B., Janowska J Fau - Olszanecka-Glinianowicz, M., Olszanecka-Glinianowicz M Fau - Zurakowski, A., & Zurakowski, A. Serum concentrations of TNF-alpha and soluble TNF-alpha receptors in obesity.
    Zarghi, A., & Arfaei, S. (2011). Selective COX-2 Inhibitors: A Review of Their Structure-Activity Relationships. Iran J Pharm Res, 10(4), 655-68
    Zarzynska, J. M. (2014). Two faces of TGF-beta1 in breast cancer. Mediators Inflamm, 2014, 141747. doi:10.1155/2014/141747
    Zelenay, S., van der Veen, A. G., Bottcher, J. P., Snelgrove, K. J., Rogers, N., Acton, S. E., & Reis e Sousa, C. (2015). Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity. Cell, 162(6), 1257-1270. doi:10.1016/j.cell.2015.08.015
    Zhang, B., Zhang, Y., Yao, G., Gao, J., Yang, B., Zhao, Y., & Gao, J. (2012). M2-polarized macrophages promote metastatic behavior of Lewis lung carcinoma cells by inducing vascular endothelial growth factor-C expression. Clinics, 67(8), 901-906. doi:10.6061/clinics/2012(08)08
    Zhang, X., Tian, W., Cai, X., Wang, X., Dang, W., Tang, H., & Chen, T. (2013). Hydrazinocurcumin Encapsuled nanoparticles "re-educate" tumor-associated macrophages and exhibit anti-tumor effects on breast cancer following STAT3 suppression. PLoS One, 8(6), e65896. doi:10.1371/journal.pone.0065896
    Zheng, Q., Dunlap, S. M., Zhu, J., Downs-Kelly, E., Rich, J., Hursting, S. D., & Reizes, O. (2011). Leptin deficiency suppresses MMTV-Wnt-1 mammary tumor growth in obese mice and abrogates tumor initiating cell survival. Endocr Relat Cancer, 18(4), 491-503. doi: 10.1530/ERC-11-0102
    Zhou, Y., Liu, B. L., Liu, K., Tang, N., Huang, J., An, Y., & Li, L. (2008). Establishment of the insulin resistance induced by inflammatory response in 3T3-L1 preadipocytes cell line. Inflammation, 31(5), 355-364. doi:10.1007/s10753-008-9086-y

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