{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:35:13Z","timestamp":1792784113463,"version":"4.5.0"},"reference-count":99,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:00:00Z","timestamp":1579651200000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Medical University of Lodz","id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr. Treat. Options in Oncol."],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Opinion statement<\/jats:title>\n                  <jats:p>So far, opioids have been successfully used to reduce cancer pain in patients in order to improve their quality of life. However, the use of opioids leads to numerous side effects such as constipation, drowsiness, nausea, itching, increased sweating and hormonal changes. In this review, we described the action of opioids in several molecular pathways significant for maintenance of the intestinal homeostasis including the impact on the intestinal epithelium integrity, changes in microbiome composition, modulation of the immune system or induction of apoptosis and inhibition of angiogenesis. We summed up the role of individual opioids in the processes involved in the growth and development of cancer and elucidated if targeting opioid receptors may constitute novel therapeutic option in colon cancer.<\/jats:p>","DOI":"10.1007\/s11864-019-0699-1","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T02:02:50Z","timestamp":1579658570000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Opioids in Cancer Development, Progression and Metastasis: Focus on Colorectal Cancer"],"prefix":"10.1007","volume":"21","author":[{"given":"Adrian","family":"Szczepaniak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Fichna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Zieli\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,22]]},"reference":[{"key":"699_CR1","unstructured":"\u2022 Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the Global Burden of Disease Study. JAMA Oncol. 2017;3(4):524\u201348 It is a comprehensive analysis (performed using Global Burden of Disease methodology) of mortality, incidence, years lived with disability, years of life lost, and disability-adjusted life-years for 32 cancers in 195 countries and territories from 1990 to 2015."},{"issue":"6","key":"699_CR2","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1053\/j.gastro.2010.01.057","volume":"138","author":"AT Chan","year":"2010","unstructured":"Chan AT, Giovannucci EL. Primary prevention of colorectal cancer. Gastroenterology. 2010;138(6):2029\u201343.","journal-title":"Gastroenterology."},{"issue":"3","key":"699_CR3","first-page":"105","volume":"7","author":"AR Marley","year":"2016","unstructured":"Marley AR, Nan H. Epidemiology of colorectal cancer. Int J Mol Epidemiol Genet. 2016;7(3):105\u201314.","journal-title":"Int J Mol Epidemiol Genet"},{"issue":"3","key":"699_CR4","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.critrevonc.2012.09.014","volume":"86","author":"Jayshree Mishra","year":"2013","unstructured":"Mishra J, Drummond J, Quazi SH, Karanki SS, Shaw JJ, Chen B, et al. Prospective of colon cancer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis. Crit Rev Oncol Hematol. 2013:232\u201350.","journal-title":"Critical Reviews in Oncology\/Hematology"},{"issue":"3","key":"699_CR5","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S0165-0173(01)00160-6","volume":"38","author":"IS Zagon","year":"2002","unstructured":"Zagon IS, Verderame MF, McLaughlin PJ. The biology of the opioid growth factor receptor (OGFr). Brain Res Brain Res Rev. 2002;38(3):351\u201376.","journal-title":"Brain Res Brain Res Rev"},{"issue":"1","key":"699_CR6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.2478\/s11535-010-0097-y","volume":"6","author":"K Gach","year":"2011","unstructured":"Gach K, Szemraj J, Stasikowska-Kanicka O, Danilewicz M, Janecka A. Opioid-receptor gene expression and localization in cancer cells. Open Life Sci. 2011;6(1):10\u20135.","journal-title":"Open Life Sci"},{"issue":"5","key":"699_CR7","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/bjc.2014.384","volume":"111","author":"J W Boland","year":"2014","unstructured":"\u2022 Boland JW, McWilliams K, Ahmedzai SH, Pockley AG. Effects of opioids on immunologic parameters that are relevant to anti-tumour immune potential in patients with cancer: a systematic literature review. Br J Cancer. 2014:866\u201373 This interesting review summed up a knowledge about impact of different opioids on anti-tumour immunity and it can be found how difficult is to manage with drug therapy using opioids in patients with cancer.","journal-title":"British Journal of Cancer"},{"issue":"4","key":"699_CR8","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S1082-3174(99)70012-7","volume":"8","author":"R Maneckjee","year":"1999","unstructured":"Maneckjee R. Anticancer effects of therapeutic opioids. Pain Forum. 1999;8(4):213\u20135.","journal-title":"Pain Forum"},{"issue":"9","key":"699_CR9","first-page":"567","volume":"18","author":"M Akbari","year":"2015","unstructured":"Akbari M, Naghibzadeh-Tahami A, Khanjani N, Baneshi MR, Kamali E, Hesampour M, et al. Opium as a risk factor for bladder cancer: a population-based case-control study in Iran. Arch Iran Med. 2015;18(9):567\u201371.","journal-title":"Arch Iran Med"},{"issue":"2","key":"699_CR10","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/ijc.28018","volume":"133","author":"R Shakeri","year":"2013","unstructured":"Shakeri R, Malekzadeh R, Etemadi A, Nasrollahzadeh D, Aghcheli K, Sotoudeh M, et al. Opium: an emerging risk factor for gastric adenocarcinoma. Int J Cancer. 2013;133(2):455\u201361.","journal-title":"Int J Cancer"},{"issue":"5","key":"699_CR11","doi-asserted-by":"crossref","first-page":"e505","DOI":"10.1097\/SCS.0000000000001089","volume":"25","author":"E Razmpa","year":"2014","unstructured":"Razmpa E, Saedi B, Motiee-Langroudi M, Garajei A, Hoseinpor S, Motamedi MHK. Opium usage as an etiologic factor of oral cavity cancer. J Craniofac Surg. 2014;25(5):e505\u20137.","journal-title":"J Craniofac Surg"},{"issue":"3","key":"699_CR12","doi-asserted-by":"crossref","first-page":"e32711","DOI":"10.1371\/journal.pone.0032711","volume":"7","author":"R Shakeri","year":"2012","unstructured":"Shakeri R, Kamangar F, Nasrollahzadeh D, Nouraie M, Khademi H, Etemadi A, et al. Is opium a real risk factor for esophageal cancer or just a methodological artifact? hospital and neighborhood controls in case-control studies. PLoS One. 2012;7(3):e32711.","journal-title":"PLoS One"},{"issue":"2","key":"699_CR13","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/s10620-006-3132-0","volume":"51","author":"L Frenklakh","year":"2006","unstructured":"Frenklakh L, Bhat RS, Bhaskaran M, Sharma S, Sharma M, Dinda A, et al. Morphine-induced degradation of the host defense barrier. Dig Dis Sci. 2006;51(2):318\u201325.","journal-title":"Dig Dis Sci"},{"issue":"1","key":"699_CR14","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.surg.2005.07.009","volume":"139","author":"Y Harari","year":"2006","unstructured":"Harari Y, Weisbrodt NW, Moody FG. The effect of morphine on mast cell-mediated mucosal permeability. Surgery. 2006;139(1):54\u201360.","journal-title":"Surgery."},{"issue":"2","key":"699_CR15","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1007\/s12029-017-0050-7","volume":"49","author":"Mohammed Azeez Alzaidi","year":"2018","unstructured":"Alzaidi MA, Arab HA, Amanpour S, Shirkoohi R, Muhammadnejad S, Sasani F. Correction to: Opium consumption and the incidence of cancer: does opium account as an emerging risk factor for gastrointestinal cancer? J Gastrointest Cancer. 2018. https:\/\/doi.org\/10.1007\/s12029-017-0050-7.","journal-title":"Journal of Gastrointestinal Cancer"},{"issue":"10","key":"699_CR16","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1078\/0344-0338-00146","volume":"197","author":"G Pasz-Walczak","year":"2001","unstructured":"Pasz-Walczak G, Kordek R, Faflik M. P21 (WAF1) expression in colorectal cancer: correlation with P53 and cyclin D1 expression, clinicopathological parameters and prognosis. Pathol Res Pract. 2001;197(10):683\u20139.","journal-title":"Pathol Res Pract"},{"key":"699_CR17","doi-asserted-by":"crossref","unstructured":"\u2022 Chelakkot C, Ghim J, Ryu SH. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med. 2018;50(8) An interesting review on the intestinal epithelial barrier.","DOI":"10.1038\/s12276-018-0126-x"},{"issue":"1","key":"699_CR18","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1177\/0192623316679898","volume":"45","author":"F Wang","year":"2017","unstructured":"Wang F, Roy S. Gut homeostasis, microbial dysbiosis, and opioids. Toxicol Pathol. 2017;45(1):150\u20136.","journal-title":"Toxicol Pathol"},{"issue":"5","key":"699_CR19","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1007\/s10875-008-9208-1","volume":"28","author":"SD Mahajan","year":"2008","unstructured":"Mahajan SD, Aalinkeel R, Sykes DE, Reynolds JL, Bindukumar B, Fernandez SF, et al. Tight junction regulation by morphine and HIV-1 tat modulates blood\u2013brain barrier permeability. J Clin Immunol. 2008;28(5):528\u201341.","journal-title":"J Clin Immunol"},{"issue":"1","key":"699_CR20","doi-asserted-by":"crossref","first-page":"e54040","DOI":"10.1371\/journal.pone.0054040","volume":"8","author":"J Meng","year":"2013","unstructured":"Meng J, Yu H, Ma J, Wang J, Banerjee S, Charboneau R, et al. Morphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner. Buch SJ, editor. PLoS One. 2013;8(1):e54040.","journal-title":"PLoS One"},{"key":"699_CR21","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.jss.2017.05.099","volume":"219","author":"BD Bauman","year":"2017","unstructured":"\u2022\u2022 Bauman BD, Meng J, Zhang L, Louiselle A, Zheng E, Banerjee S, et al. Enteric glial-mediated enhancement of intestinal barrier integrity is compromised by morphine. J Surg Res. 2017;219:214\u201321 An important involvement of the maintenance of intestinal epithelium integrity.","journal-title":"J Surg Res"},{"issue":"9","key":"699_CR22","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1248\/bpb.32.1571","volume":"32","author":"T Okura","year":"2009","unstructured":"Okura T, Ozawa T, Ibe M, Taki Y, Kimura M, Kagawa Y, et al. Effects of repeated morphine treatment on the antinociceptive effects, intestinal absorption, and efflux from intestinal epithelial cells of morphine. Biol Pharm Bull. 2009;32(9):1571\u20135.","journal-title":"Biol Pharm Bull"},{"issue":"1","key":"699_CR23","doi-asserted-by":"crossref","first-page":"3596","DOI":"10.1038\/s41598-018-21915-8","volume":"8","author":"F Wang","year":"2018","unstructured":"\u2022\u2022 Wang F, Meng J, Zhang L, Johnson T, Chen C, Roy S. Morphine induces changes in the gut microbiome and metabolome in a morphine dependence model. Sci Rep. 2018;8(1):3596 In this paper authors indicated that morphine induced distinct alterations in the gut microbiome and metabolome, contributed to negative consequences combined with opioid administration.","journal-title":"Sci Rep"},{"key":"699_CR24","doi-asserted-by":"crossref","first-page":"175628481878360","DOI":"10.1177\/1756284818783606","volume":"11","author":"CV de Almeida","year":"2018","unstructured":"de Almeida CV, Taddei A, Amedei A. The controversial role of enterococcus faecalis in colorectal cancer. Ther Adv Gastroenterol. 2018;11:1756284818783606.","journal-title":"Ther Adv Gastroenterol"},{"issue":"3","key":"699_CR25","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1093\/carcin\/23.3.529","volume":"23","author":"MM Huycke","year":"2002","unstructured":"Huycke MM, Abrams V, Moore DR. Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis. 2002;23(3):529\u201336.","journal-title":"Carcinogenesis."},{"issue":"24","key":"699_CR26","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1093\/jnci\/djt300","volume":"105","author":"J Ahn","year":"2013","unstructured":"Ahn J, Sinha R, Pei Z, Dominianni C, Wu J, Shi J, et al. Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst. 2013;105(24):1907\u201311.","journal-title":"J Natl Cancer Inst"},{"issue":"2","key":"699_CR27","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1101\/gr.126516.111","volume":"22","author":"M Castellarin","year":"2012","unstructured":"Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22(2):299\u2013306.","journal-title":"Genome Res"},{"issue":"4","key":"699_CR28","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.tem.2011.01.002","volume":"22","author":"T Greiner","year":"2011","unstructured":"Greiner T, B\u00e4ckhed F. Effects of the gut microbiota on obesity and glucose homeostasis. Trends Endocrinol Metab. 2011;22(4):117\u201323.","journal-title":"Trends Endocrinol Metab"},{"issue":"1","key":"699_CR29","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1146\/annurev-immunol-020711-074937","volume":"30","author":"K Honda","year":"2012","unstructured":"Honda K, Littman DR. The microbiome in infectious disease and inflammation. Annu Rev Immunol. 2012;30(1):759\u201395.","journal-title":"Annu Rev Immunol"},{"issue":"1","key":"699_CR30","first-page":"5","volume":"1","author":"X Liang","year":"2016","unstructured":"Liang X, Liu R, Chen C, Ji F, Li T. Opioid system modulates the immune function: a review. Transl Perioper Pain Med. 2016;1(1):5\u201313.","journal-title":"Transl Perioper Pain Med"},{"key":"699_CR31","doi-asserted-by":"crossref","unstructured":"Baldini A, Von Korff M, Lin EHB. A review of potential adverse effects of long-term opioid therapy: a practitioner\u2019s guide. Prim Care Companion CNS Disord. 2012;14(3).","DOI":"10.4088\/PCC.11m01326"},{"issue":"1","key":"699_CR32","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.psychres.2014.12.053","volume":"226","author":"Y-Y Chan","year":"2015","unstructured":"Chan Y-Y, Yang S-N, Lin J-C, Chang J-L, Lin J-G, Lo W-Y. Inflammatory response in heroin addicts undergoing methadone maintenance treatment. Psychiatry Res. 2015;226(1):230\u20134.","journal-title":"Psychiatry Res"},{"issue":"6","key":"699_CR33","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1007\/s10787-018-0538-1","volume":"26","author":"N Fakhraei","year":"2018","unstructured":"\u2022 Fakhraei N, Javadian N, Rahimian R, Nili F, Rahimi N, Hashemizadeh S, et al. Involvement of central opioid receptors in protective effects of methadone on experimental colitis in rats. Inflammopharmacology. 2018;26(6):1399\u2013413 In this study it was found that methadone may induce anti-inflammatory action during colonic inflammation through opioid receptors located mainly in the central nervous system.","journal-title":"Inflammopharmacology"},{"issue":"4","key":"699_CR34","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.3892\/etm.2016.3647","volume":"12","author":"J-Y Du","year":"2016","unstructured":"Du J-Y, Liang Y, Fang J-F, Jiang Y-L, Shao X-M, He X-F, et al. Effect of systemic injection of heterogenous and homogenous opioids on peripheral cellular immune response in rats with bone cancer pain: a comparative study. Exp Ther Med. 2016;12(4):2568\u201376.","journal-title":"Exp Ther Med"},{"issue":"3","key":"699_CR35","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/sj.npp.1301440","volume":"33","author":"EM Weerts","year":"2008","unstructured":"Weerts EM, Kim YK, Wand GS, Dannals RF, Lee JS, Frost JJ, et al. Differences in \u03b4- and \u03bc-opioid receptor blockade measured by positron emission tomography in naltrexone-treated recently abstinent alcohol-dependent subjects. Neuropsychopharmacology. 2008;33(3):653\u201365.","journal-title":"Neuropsychopharmacology."},{"issue":"13","key":"699_CR36","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1056\/NEJMoa1505409","volume":"374","author":"JD Lee","year":"2016","unstructured":"Lee JD, Friedmann PD, Kinlock TW, Nunes EV, Boney TY, Hoskinson RA, et al. Extended-release naltrexone to prevent opioid relapse in criminal justice offenders. N Engl J Med. 2016;374(13):1232\u201342.","journal-title":"N Engl J Med"},{"key":"699_CR37","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.intimp.2016.08.015","volume":"39","author":"Z Yi","year":"2016","unstructured":"Yi Z, Guo S, Hu X, Wang X, Zhang X, Griffin N, et al. Functional modulation on macrophage by low dose naltrexone (LDN). Int Immunopharmacol. 2016;39:397\u2013402.","journal-title":"Int Immunopharmacol"},{"issue":"17","key":"699_CR38","doi-asserted-by":"crossref","first-page":"4275","DOI":"10.3748\/wjg.v22.i17.4275","volume":"22","author":"M Kajihara","year":"2016","unstructured":"Kajihara M, Takakura K, Kanai T, Ito Z, Saito K, Takami S, et al. Dendritic cell-based cancer immunotherapy for colorectal cancer. World J Gastroenterol. 2016;22(17):4275\u201386.","journal-title":"World J Gastroenterol"},{"issue":"10","key":"699_CR39","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1007\/s00262-012-1221-9","volume":"61","author":"J Liu","year":"2012","unstructured":"Liu J, Chen W, Meng J, Lu C, Wang E, Shan F, et al. Induction on differentiation and modulation of bone marrow progenitor of dendritic cell by methionine enkephalin (MENK). Cancer Immunol Immunother. 2012;61(10):1699\u2013711.","journal-title":"Cancer Immunol Immunother"},{"issue":"3","key":"699_CR40","first-page":"492","volume":"82","author":"B Beilin","year":"1996","unstructured":"Beilin B, Shavit Y, Hart J, Mordashov B, Cohn S, Notti I, et al. Effects of anesthesia based on large versus small doses of fentanyl on natural killer cell cytotoxicity in the perioperative period. Anesth Analg. 1996;82(3):492\u20137.","journal-title":"Anesth Analg"},{"issue":"1","key":"699_CR41","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1213\/00000539-200201000-00018","volume":"94","author":"MP Yeager","year":"2002","unstructured":"Yeager MP, Procopio MA, DeLeo JA, Arruda JL, Hildebrandt L, Howell AL. Intravenous fentanyl increases natural killer cell cytotoxicity and circulating CD16(+) lymphocytes in humans. Anesth Analg. 2002;94(1):94\u20139.","journal-title":"Anesth Analg"},{"key":"699_CR42","unstructured":"Odunayo A, Dodam JR, Kerl ME, DeClue AE. Immunomodulatory effects of opioids. J Vet Emerg Crit Care. 2010."},{"issue":"1","key":"699_CR43","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1213\/00000539-199801000-00033","volume":"86","author":"S Palm","year":"1998","unstructured":"Palm S, Lehzen S, Mignat C, Steinmann J, Leimenstoll G, Maier C. Does prolonged oral treatment with sustained-release morphine tablets influence immune function? Anesth Analg. 1998;86(1):166\u201372.","journal-title":"Anesth Analg"},{"issue":"12","key":"699_CR44","first-page":"4561","volume":"31","author":"C Makimura","year":"2011","unstructured":"Makimura C, Arao T, Matsuoka H, Takeda M, Kiyota H, Tsurutani J, et al. Prospective study evaluating the plasma concentrations of twenty-six cytokines and response to morphine treatment in cancer patients. Anticancer Res. 2011;31(12):4561\u20138.","journal-title":"Anticancer Res"},{"issue":"7","key":"699_CR45","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1177\/1049909112469823","volume":"30","author":"M Suzuki","year":"2013","unstructured":"Suzuki M, Sakurada T, Gotoh K, Watanabe S, Satoh N. Correlation between the administration of morphine or oxycodone and the development of infections in patients with cancer pain. Am J Hosp Palliat Med. 2013;30(7):712\u20136.","journal-title":"Am J Hosp Palliat Med"},{"key":"699_CR46","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.bbi.2014.06.011","volume":"42","author":"LM Molina-Mart\u00ednez","year":"2014","unstructured":"Molina-Mart\u00ednez LM, Gonz\u00e1lez-Espinosa C, Cruz SL. Dissociation of immunosuppressive and nociceptive effects of fentanyl, but not morphine, after repeated administration in mice: fentanyl-induced sensitization to LPS. Brain Behav Immun. 2014;42:60\u20134.","journal-title":"Brain Behav Immun"},{"issue":"6","key":"699_CR47","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.bbi.2007.01.001","volume":"21","author":"S Franchi","year":"2007","unstructured":"Franchi S, Panerai AE, Sacerdote P. Buprenorphine ameliorates the effect of surgery on hypothalamus\u2013pituitary\u2013adrenal axis, natural killer cell activity and metastatic colonization in rats in comparison with morphine or fentanyl treatment. Brain Behav Immun. 2007;21(6):767\u201374.","journal-title":"Brain Behav Immun"},{"issue":"4","key":"699_CR48","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1159\/000078444","volume":"11","author":"Y Shavit","year":"2004","unstructured":"Shavit Y, Ben-Eliyahu S, Zeidel A, Beilin B. Effects of fentanyl on natural killer cell activity and on resistance to tumor metastasis in rats. Neuroimmunomodulation. 2004;11(4):255\u201360.","journal-title":"Neuroimmunomodulation."},{"issue":"6","key":"699_CR49","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.7314\/APJCP.2015.16.6.2129","volume":"16","author":"S Goldar","year":"2015","unstructured":"Goldar S, Khaniani MS, Derakhshan SM, Baradaran B. Molecular mechanisms of apoptosis and roles in cancer development and treatment. Asian Pac J Cancer Prev. 2015;16(6):2129\u201344.","journal-title":"Asian Pac J Cancer Prev"},{"issue":"53","key":"699_CR50","doi-asserted-by":"crossref","first-page":"8590","DOI":"10.1038\/sj.onc.1207102","volume":"22","author":"S Cory","year":"2003","unstructured":"Cory S, Huang DCS, Adams JM. The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene. 2003;22(53):8590\u2013607.","journal-title":"Oncogene."},{"issue":"2","key":"699_CR51","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3892\/etm.2016.3346","volume":"12","author":"M Tian","year":"2016","unstructured":"Tian M, Jin L, Li R, Zhu S, Ji M, Li W. Comparison of oxycodone and morphine on the proliferation, apoptosis and expression of related molecules in the A549 human lung adenocarcinoma cell line. Exp Ther Med. 2016;12(2):559\u201366.","journal-title":"Exp Ther Med"},{"issue":"2","key":"699_CR52","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/anae.13331","volume":"71","author":"YJ Xu","year":"2016","unstructured":"Xu YJ, Li SY, Cheng Q, Chen WK, Wang SL, Ren Y, et al. Effects of anaesthesia on proliferation, invasion and apoptosis of LoVo colon cancer cells in vitro. Anaesthesia. 2016;71(2):147\u201354.","journal-title":"Anaesthesia."},{"issue":"8","key":"699_CR53","first-page":"1846","volume":"63","author":"I Tegeder","year":"2003","unstructured":"Tegeder I, Gr\u00f6sch S, Schmidtko A, H\u00e4ussler A, Schmidt H, Niederberger E, et al. G protein-independent G1 cell cycle block and apoptosis with morphine in adenocarcinoma cells: involvement of p53 phosphorylation. Cancer Res. 2003;63(8):1846\u201352.","journal-title":"Cancer Res"},{"issue":"2","key":"699_CR54","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0143-4179(03)00007-6","volume":"37","author":"IS Zagon","year":"2003","unstructured":"Zagon IS, McLaughlin PJ. Opioids and the apoptotic pathway in human cancer cells. Neuropeptides. 2003;37(2):79\u201388.","journal-title":"Neuropeptides."},{"issue":"3","key":"699_CR55","first-page":"735","volume":"18","author":"N Kocak","year":"2017","unstructured":"Kocak N, Ozen F, Yildirim IH, Duran Y. Fentanyl inhibits tumorigenesis from human breast stem cells by inducing apoptosis. Asian Pac J Cancer Prev. 2017;18(3):735\u20139.","journal-title":"Asian Pac J Cancer Prev"},{"key":"699_CR56","doi-asserted-by":"crossref","first-page":"144030","DOI":"10.1016\/j.gene.2019.144030","volume":"718","author":"U \u00d6zg\u00fcrb\u00fcz","year":"2019","unstructured":"\u00d6zg\u00fcrb\u00fcz U, Genc\u00fcr S, Kurt F\u00d6, \u00d6zkalkanl\u0131 M, Vatansever HS. The effects of tramadol on cancer stem cells and metabolic changes in colon carcinoma cells lines. Gene. 2019;718:144030.","journal-title":"Gene."},{"key":"699_CR57","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.2147\/OTT.S161109","volume":"11","author":"L Xia","year":"2018","unstructured":"Xia L, Tan S, Zhou Y, Lin J, Wang H, Oyang L, et al. Role of the NF\u03baB-signaling pathway in cancer. Onco Targets Ther. 2018;11:2063\u201373.","journal-title":"Onco Targets Ther"},{"issue":"1","key":"699_CR58","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1423-0127-20-3","volume":"20","author":"W-C Huang","year":"2013","unstructured":"Huang W-C, Hung M-C. Beyond NF-\u03baB activation: nuclear functions of I\u03baB kinase \u03b1. J Biomed Sci. 2013;20(1):3.","journal-title":"J Biomed Sci"},{"issue":"5","key":"699_CR59","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646\u201374.","journal-title":"Cell."},{"issue":"9","key":"699_CR60","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.4049\/jimmunol.1300320","volume":"191","author":"C Borner","year":"2013","unstructured":"Borner C, Kraus J. Inhibition of NF- B by opioids in T cells. J Immunol. 2013;191(9):4640\u20137.","journal-title":"J Immunol"},{"issue":"3","key":"699_CR61","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.4049\/jimmunol.1400106","volume":"194","author":"S Qiu","year":"2015","unstructured":"Qiu S, Feng Y, LeSage G, Zhang Y, Stuart C, He L, et al. Chronic morphine-induced microRNA-124 promotes microglial immunosuppression by modulating P65 and TRAF6. J Immunol. 2015;194(3):1021\u201330.","journal-title":"J Immunol"},{"issue":"4","key":"699_CR62","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1124\/mol.111.076620","volume":"81","author":"C Borner","year":"2012","unstructured":"Borner C, Hollt V, Kraus J. Mechanisms of the inhibition of nuclear factor- B by morphine in neuronal cells. Mol Pharmacol. 2012;81(4):587\u201397.","journal-title":"Mol Pharmacol"},{"issue":"6","key":"699_CR63","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1097\/00000542-200006000-00027","volume":"92","author":"ID Welters","year":"2000","unstructured":"Welters ID, Menzebach A, Goumon Y, Cadet P, Menges T, Hughes TK, et al. Morphine inhibits NF-kappaB nuclear binding in human neutrophils and monocytes by a nitric oxide-dependent mechanism. Anesthesiology. 2000;92(6):1677\u201384.","journal-title":"Anesthesiology."},{"issue":"8","key":"699_CR64","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/j.intimp.2006.03.017","volume":"6","author":"JA Beltran","year":"2006","unstructured":"Beltran JA, Peek J, Chang SL. Expression and regulation of the mu opioid peptide receptor in TPA-differentiated HL-60 promyelocytic leukemia cells. Int Immunopharmacol. 2006;6(8):1331\u201340.","journal-title":"Int Immunopharmacol"},{"issue":"2","key":"699_CR65","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S1734-1140(10)70262-0","volume":"62","author":"N Ghosh","year":"2010","unstructured":"Ghosh N, Chaki R, Mandal V, Mandal SC. COX-2 as a target for cancer chemotherapy. Pharmacol Rep. 2010;62(2):233\u201344.","journal-title":"Pharmacol Rep"},{"issue":"1","key":"699_CR66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/187152408783790604","volume":"8","author":"A Capasso","year":"2008","unstructured":"Capasso A. The effect of morphine on the expression of COX-2 and iNOS enzymes. Cent Nerv Syst Agents Med Chem. 2008;8(1):1\u20139.","journal-title":"Cent Nerv Syst Agents Med Chem"},{"issue":"8","key":"699_CR67","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1111\/j.1742-4658.2009.06934.x","volume":"276","author":"SA Waldman","year":"2009","unstructured":"Waldman SA, Terzic A. A study of microRNAs in silico and in vivo: diagnostic and therapeutic applications in cancer. FEBS J. 2009;276(8):2157\u201364.","journal-title":"FEBS J"},{"issue":"1","key":"699_CR68","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00384-012-1528-1","volume":"28","author":"T Zhou","year":"2013","unstructured":"Zhou T, Zhang G, Liu Z, Xia S, Tian H. Overexpression of miR-92a correlates with tumor metastasis and poor prognosis in patients with colorectal cancer. Int J Color Dis. 2013;28(1):19\u201324.","journal-title":"Int J Color Dis"},{"issue":"7","key":"699_CR69","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1111\/j.1742-4658.2012.08519.x","volume":"279","author":"W-Q Kong","year":"2012","unstructured":"Kong W-Q, Bai R, Liu T, Cai C-L, Liu M, Li X, et al. MicroRNA-182 targets cAMP-responsive element-binding protein\u20031 and suppresses cell growth in human gastric adenocarcinoma. FEBS J. 2012;279(7):1252\u201360.","journal-title":"FEBS J"},{"issue":"2","key":"699_CR70","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/path.4000","volume":"228","author":"Z Liu","year":"2012","unstructured":"Liu Z, Liu J, Segura MF, Shao C, Lee P, Gong Y, et al. MiR-182 overexpression in tumourigenesis of high-grade serous ovarian carcinoma. J Pathol. 2012;228(2):204\u201315.","journal-title":"J Pathol"},{"issue":"6","key":"699_CR71","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/ncb2769","volume":"15","author":"N Pencheva","year":"2013","unstructured":"Pencheva N, Tavazoie SF. Control of metastatic progression by microRNA regulatory networks. Nat Cell Biol. 2013;15(6):546\u201354.","journal-title":"Nat Cell Biol"},{"issue":"1","key":"699_CR72","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev.med.59.053006.104707","volume":"60","author":"R Garzon","year":"2009","unstructured":"Garzon R, Calin GA, Croce CM. MicroRNAs in cancer. Annu Rev Med. 2009;60(1):167\u201379.","journal-title":"Annu Rev Med"},{"issue":"1","key":"699_CR73","first-page":"227","volume":"8","author":"XL Zhang","year":"2015","unstructured":"Zhang XL, Chen ML, Zhou SL. Fentanyl inhibits proliferation and invasion of colorectal cancer via \u03b2-catenin. Int J Clin Exp Pathol. 2015;8(1):227\u201335.","journal-title":"Int J Clin Exp Pathol"},{"issue":"5","key":"699_CR74","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s00384-013-1674-0","volume":"28","author":"H Liu","year":"2013","unstructured":"Liu H, Du L, Wen Z, Yang Y, Li J, Wang L, et al. Up-regulation of miR-182 expression in colorectal cancer tissues and its prognostic value. Int J Color Dis. 2013;28(5):697\u2013703.","journal-title":"Int J Color Dis"},{"issue":"1","key":"699_CR75","first-page":"459","volume":"16","author":"N Wang","year":"2018","unstructured":"Wang N, Zhang Z, Lv J. Fentanyl inhibits proliferation and invasion via enhancing miR-302b expression in esophageal squamous cell carcinoma. Oncol Lett. 2018;16(1):459\u201366.","journal-title":"Oncol Lett"},{"issue":"2","key":"699_CR76","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1067\/mva.2000.107763b","volume":"32","author":"J Blebea","year":"2000","unstructured":"Blebea J, Mazo JE, Kihara TK, Vu J-H, McLaughlin PJ, Atnip RG, et al. Opioid growth factor modulates angiogenesis. J Vasc Surg. 2000;32(2):364\u201373.","journal-title":"J Vasc Surg"},{"issue":"1\u20133","key":"699_CR77","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.ejphar.2007.10.015","volume":"579","author":"X Dai","year":"2008","unstructured":"Dai X, Cui S, Wang T, Liu Q, Song H, Wang R. Endogenous opioid peptides, endomorphin-1 and -2 and deltorphin I, stimulate angiogenesis in the CAM assay. Eur J Pharmacol. 2008;579(1\u20133):269\u201375.","journal-title":"Eur J Pharmacol"},{"issue":"2","key":"699_CR78","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/bph.12573","volume":"172","author":"K Yamamizu","year":"2015","unstructured":"\u2022 Yamamizu K, Hamada Y, Narita M. \u03ba Opioid receptor ligands regulate angiogenesis in development and in tumours. Br J Pharmacol. 2015;172(2):268\u201376 In this study it was found that methadone may induce anti-inflammatory action during colonic inflammation through opioid receptors located mainly in the central nervous system.","journal-title":"Br J Pharmacol"},{"issue":"15","key":"699_CR79","doi-asserted-by":"crossref","first-page":"25783","DOI":"10.18632\/oncotarget.15419","volume":"8","author":"M Ondrovics","year":"2017","unstructured":"Ondrovics M, Hoelbl-Kovacic A, Fux DA. Opioids: modulators of angiogenesis in wound healing and cancer. Oncotarget. 2017;8(15):25783\u201396.","journal-title":"Oncotarget."},{"issue":"Suppl 1","key":"699_CR80","doi-asserted-by":"crossref","first-page":"i4","DOI":"10.1093\/bja\/aeu090","volume":"113","author":"J Nguyen","year":"2014","unstructured":"Nguyen J, Luk K, Vang D, Soto W, Vincent L, Robiner S, et al. Morphine stimulates cancer progression and mast cell activation and impairs survival in transgenic mice with breast cancer. Br J Anaesth. 2014;113(Suppl 1):i4\u201313.","journal-title":"Br J Anaesth"},{"issue":"2","key":"699_CR81","doi-asserted-by":"crossref","first-page":"984","DOI":"10.2353\/ajpath.2010.090621","volume":"177","author":"L Koodie","year":"2010","unstructured":"Koodie L, Ramakrishnan S, Roy S. Morphine suppresses tumor angiogenesis through a HIF-1alpha\/p38MAPK pathway. Am J Pathol. 2010;177(2):984\u201397.","journal-title":"Am J Pathol"},{"issue":"15","key":"699_CR82","first-page":"4491","volume":"62","author":"K Gupta","year":"2002","unstructured":"Gupta K, Kshirsagar S, Chang L, Schwartz R, Law PY, Yee D, et al. Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth. Cancer Res. 2002;62(15):4491\u20138.","journal-title":"Cancer Res"},{"issue":"2","key":"699_CR83","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.cellimm.2010.08.002","volume":"265","author":"JL Martin","year":"2010","unstructured":"Martin JL, Charboneau R, Barke RA, Roy S. Chronic morphine treatment inhibits LPS-induced angiogenesis: implications in wound healing. Cell Immunol. 2010;265(2):139\u201345.","journal-title":"Cell Immunol"},{"issue":"4","key":"699_CR84","doi-asserted-by":"crossref","first-page":"262","DOI":"10.5812\/aapm.4529","volume":"1","author":"M Moradi","year":"2012","unstructured":"Moradi M, Esmaeili S, Shoar S, Safari S. Use of oxycodone in pain management. Anesthesiol Pain Med. 2012;1(4):262\u20134.","journal-title":"Anesthesiol Pain Med"},{"issue":"2","key":"699_CR85","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.bbcan.2009.07.006","volume":"1796","author":"Thomas R. Geiger","year":"2009","unstructured":"Geiger TR, Peeper DS. Metastasis mechanisms. Biochim Biophys Acta Rev Cancer. 2009:293\u2013308.","journal-title":"Biochimica et Biophysica Acta (BBA) - Reviews on Cancer"},{"issue":"6","key":"699_CR86","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1002\/jcb.24480","volume":"114","author":"KD Fagan-Solis","year":"2013","unstructured":"Fagan-Solis KD, Schneider SS, Pentecost BT, Bentley BA, Otis CN, Gierthy JF, et al. The RhoA pathway mediates MMP-2 and MMP-9-independent invasive behavior in a triple-negative breast cancer cell line. J Cell Biochem. 2013;114(6):1385\u201394.","journal-title":"J Cell Biochem"},{"issue":"4","key":"699_CR87","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/path.1396","volume":"200","author":"Jean A Engbring","year":"2003","unstructured":"Engbring JA, Kleinman HK. The basement membrane matrix in malignancy. J Pathol. 2003:465\u201370.","journal-title":"The Journal of Pathology"},{"issue":"1\u20132","key":"699_CR88","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0304-3835(02)00360-9","volume":"187","author":"Y Harimaya","year":"2002","unstructured":"Harimaya Y, Koizumi K, Andoh T, Nojima H, Kuraishi Y, Saiki I. Potential ability of morphine to inhibit the adhesion, invasion and metastasis of metastatic colon 26-L5 carcinoma cells. Cancer Lett. 2002;187(1\u20132):121\u20137.","journal-title":"Cancer Lett"},{"issue":"2","key":"699_CR89","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s10620-007-9897-y","volume":"53","author":"G Nylund","year":"2008","unstructured":"Nylund G, Pettersson A, Bengtsson C, Khorram-Manesh A, Nordgren S, Delbro DS. Functional expression of \u03bc-opioid receptors in the human colon cancer cell line, HT-29, and their localization in human colon. Dig Dis Sci. 2008;53(2):461\u20136.","journal-title":"Dig Dis Sci"},{"issue":"2","key":"699_CR90","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00210-019-01613-6","volume":"392","author":"S Khabbazi","year":"2019","unstructured":"\u2022 Khabbazi S, Hassanshahi M, Hassanshahi A, Peymanfar Y, Su Y-W, Xian CJ. Opioids and matrix metalloproteinases: the influence of morphine on MMP-9 production and cancer progression. Naunyn Schmiedeberg's Arch Pharmacol. 2019;392(2):123\u201333 In this review possible influence of opioids such as morphine on matrix metalloproteinases production through different molecular pathways has been discussed.","journal-title":"Naunyn Schmiedeberg's Arch Pharmacol"},{"issue":"4","key":"699_CR91","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/ijc.11436","volume":"107","author":"MG Tutton","year":"2003","unstructured":"Tutton MG, George ML, Eccles SA, Burton S, Swift RI, Abulafi AM. Use of plasma MMP-2 and MMP-9 levels as a surrogate for tumour expression in colorectal cancer patients. Int J Cancer. 2003;107(4):541\u201350.","journal-title":"Int J Cancer"},{"issue":"4","key":"699_CR92","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1002\/cam4.236","volume":"3","author":"JP Cata","year":"2014","unstructured":"Cata JP, Keerty V, Keerty D, Feng L, Norman PH, Gottumukkala V, et al. A retrospective analysis of the effect of intraoperative opioid dose on cancer recurrence after non-small cell lung cancer resection. Cancer Med. 2014;3(4):900\u20138.","journal-title":"Cancer Med"},{"issue":"10","key":"699_CR93","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1089\/jpm.2018.0044","volume":"21","author":"T Hasegawa","year":"2018","unstructured":"Hasegawa T, Oguri T, Osawa T, Sawa T, Osaga S, Okuyama T, et al. Opioid dose and survival of patients with incurable nonsmall cell lung cancer: a prospective cohort study. J Palliat Med. 2018;21(10):1436\u201341.","journal-title":"J Palliat Med"},{"issue":"11","key":"699_CR94","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1093\/annonc\/mdw317","volume":"27","author":"F Janku","year":"2016","unstructured":"Janku F, Johnson LK, Karp DD, Atkins JT, Singleton PA, Moss J. Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer. Ann Oncol Off J Eur Soc Med Oncol. 2016;27(11):2032\u20138.","journal-title":"Ann Oncol Off J Eur Soc Med Oncol"},{"issue":"1","key":"699_CR95","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s12904-016-0169-5","volume":"15","author":"A Sathornviriyapong","year":"2016","unstructured":"Sathornviriyapong A, Nagaviroj K, Anothaisintawee T. The association between different opioid doses and the survival of advanced cancer patients receiving palliative care. BMC Palliat Care. 2016;15(1):95.","journal-title":"BMC Palliat Care"},{"issue":"10211","key":"699_CR96","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/S0140-6736(19)32313-X","volume":"394","author":"DI Sessler","year":"2019","unstructured":"Sessler DI, Pei L, Huang Y, Fleischmann E, Marhofer P, Kurz A, et al. Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial. Lancet. 2019;394(10211):1807\u201315.","journal-title":"Lancet."},{"issue":"28","key":"699_CR97","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.2174\/1381612825666190703163329","volume":"25","author":"MW Sekandarzad","year":"2019","unstructured":"Sekandarzad MW, Doornebal C, Hollmann MW. Opiophobia in cancer biology- justified? - the role of perioperative use of opioids in cancer recurrence. Curr Pharm Des. 2019;25(28):3020\u20137.","journal-title":"Curr Pharm Des"},{"key":"699_CR98","doi-asserted-by":"crossref","first-page":"18706","DOI":"10.1038\/srep18706","volume":"6","author":"L-H Cao","year":"2016","unstructured":"Cao L-H, Li H-T, Lin W-Q, Tan H-Y, Xie L, Zhong Z-J, et al. Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts. Sci Rep. 2016;6:18706.","journal-title":"Sci Rep"},{"issue":"18","key":"699_CR99","doi-asserted-by":"crossref","first-page":"5803","DOI":"10.1158\/1078-0432.CCR-09-0811","volume":"15","author":"B He","year":"2009","unstructured":"He B, Tong X, Wang L, Wang Q, Ye H, Liu B, et al. Tramadol and flurbiprofen depress the cytotoxicity of cisplatin via their effects on gap junctions. Clin Cancer Res. 2009;15(18):5803\u201310.","journal-title":"Clin Cancer Res"}],"container-title":["Current Treatment Options in Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11864-019-0699-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11864-019-0699-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11864-019-0699-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T04:06:35Z","timestamp":1665547595000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11864-019-0699-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":99,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["699"],"URL":"https:\/\/doi.org\/10.1007\/s11864-019-0699-1","relation":{},"ISSN":["1527-2729","1534-6277"],"issn-type":[{"value":"1527-2729","type":"print"},{"value":"1534-6277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1]]},"assertion":[{"value":"22 January 2020","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This article does not contain any studies with human or animal subjects performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and Animal Rights and Informed Consent"}}],"article-number":"6"}}