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 |
相關次數: | 點閱:166 下載:7 |
分享至: |
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
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.
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