References
- Rutman RJ, Cantarow A, Paschkis KE. Studies in 2-acetylaminofluorene carcinogenesis: III. The utilization of uracil-2-C14 by preneoplastic rat liver and rat hepatoma. Cancer Res. 1954;14(2):119–123.
- Howland RD, Mycek MJ, Harvey RA, Champe PC. Lippincott's illustrated reviews: pharmacology. Philadelphia (PA): Lippincott Williams & Wilkins, 2006.
- Irish JM, Kotecha N, Nolan GP. Mapping normal and cancer cell signalling networks: towards single-cell proteomics. Nat Rev Cancer. 2006;6(2):146–155. doi:https://doi.org/10.1038/nrc1804.
- Zaniboni A. Adjuvant chemotherapy in colorectal cancer with high-dose leucovorin and fluorouracil: impact on disease-free survival and overall survival. J Clin Oncol. 1997;15(6):2432–2441. doi:https://doi.org/10.1200/JCO.1997.15.6.2432.
- Martino R, Gilard V, Desmoulin F, Malet-Martino M. Fluorine-19 or phosphorus-31 NMR spectroscopy: a suitable analytical technique for quantitative in vitro metabolic studies of fluorinated or phosphorylated drugs. J Pharm Biomed Anal. 2005;38(5):871–891. doi:https://doi.org/10.1016/j.jpba.2005.01.047.
- Diasio RB, Harris BE. Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet. 1989;16(4):215–237. doi:https://doi.org/10.2165/00003088-198916040-00002.
- Longley DB, Harkin DP, Johnston PG. 5-Fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3(5):330–338. doi:https://doi.org/10.1038/nrc1074.
- Gorlick R, Bertino JR. Clinical pharmacology and resistance to dihydrofolate reductase inhibitors. In: Jackman AL, editor. Antifolate drugs in cancer therapy. Totowa (NJ): Humana Press, 1999. p. 37–57.
- Wohlhueter RM, McIvor RS, Plagemann PG. Facilitated transport of uracil and 5-fluorouracil, and permeation of orotic acid into cultured mammalian cells. J Cell Physiol. 1980;104(3):309–319. doi:https://doi.org/10.1002/jcp.1041040305.
- Tanaka F, Fukuse T, Wada H, Fukushima M. The history, mechanism and clinical use of oral 5-fluorouracil derivative chemotherapeutic agents. Curr Pharm Biotechnol. 2000;1(2):137–164. doi:https://doi.org/10.2174/1389201003378979.
- Imoto M, Azuma H, Yamamoto I, Otagiri M, Imai T. Permeability of 5-fluorouracil and its prodrugs in Caco-2 cell monolayers: evidence for shift from paracellular to transcellular transport by prodrug formation. J Drug Deliv Sci Technol. 2009;19(1):37–41. doi:https://doi.org/10.1016/S1773-2247(09)50005-6.
- YUAsA H, Matsuhisa E, Watanabe J. Intestinal brush border transport mechanism of 5-fluorouracil in rats. Biol Pharm Bull. 1996;19(1):94–99. doi:https://doi.org/10.1248/bpb.19.94.
- Kerr IG, Zimm S, Collins JM, O'Neill D, Poplack DG. Effect of intravenous dose and schedule on cerebrospinal fluid pharmacokinetics of 5-fluorouracil in the monkey. Cancer Res. 1984;44(11):4929–4932.
- Thorn CF, Marsh S, Carrillo MW, McLeod HL, Klein TE, Altman RB. PharmGKB summary: fluoropyrimidine pathways. Pharmacogenet Genomics. 2011;21(4):237–242. doi:https://doi.org/10.1097/FPC.0b013e32833c6107.
- Miura K, Kinouchi M, Ishida K, Fujibuchi W, Naitoh T, Ogawa H, et al. 5-fu metabolism in cancer and orally-administrable 5-fu drugs. Cancers. 2010;2(3):1717–1730. doi:https://doi.org/10.3390/cancers2031717.
- Mitrovski B, Pressacco J, Mandelbaum S, Erlichman C. Biochemical effects of folate-based inhibitors of thymidylate synthase in MGH-U1 cells. Cancer Chemother Pharmacol. 1994;35(2):109–114. doi:https://doi.org/10.1007/BF00686631.
- Hagenkort A, Paulin CB, Desroses M, Sarno A, Wiita E, Mortusewicz O, et al. dUTPase inhibition augments replication defects of 5-fluorouracil. Oncotarget. 2017;8(14):23713–23726. doi:https://doi.org/10.18632/oncotarget.15785.
- An Q, Robins P, Lindahl T, Barnes DE. 5-Fluorouracil incorporated into DNA is excised by the Smug1 DNA glycosylase to reduce drug cytotoxicity. Cancer Res. 2007;67(3):940–945. doi:https://doi.org/10.1158/0008-5472.CAN-06-2960.
- Sj C, Cheng Y-C. The role of deoxyuridine triphosphate nucleotidohydrolase, uracil-DNA glycosylase, and DNA polymerase α in the metabolism of FUdR in human tumor cells. Mol Pharmacol. 1980;18(3):513–520.
- Mauro DJ, De Riel J, Tallarida RJ, Sirover MA. Mechanisms of excision of 5-fluorouracil by the uracil DNA glycosylase in normal human cells. Mol Pharm. 1993;43:854.
- Noordhuis P, Holwerda U, Van der Wilt C, Van Groeningen C, Smid K, Meijer S, et al. 5-Fluorouracil incorporation into RNA and DNA in relation to thymidylate synthase inhibition of human colorectal cancers. Ann Oncol. 2004;15(7):1025–1032. doi:https://doi.org/10.1093/annonc/mdh264.
- Spiegelman S, Sawyer R, Nayak R, Ritzi E, Stolfi R, Martin D. Improving the anti-tumor activity of 5-fluorouracil by increasing its incorporation into RNA via metabolic modulation. Proc Natl Acad Sci U S A. 1980;77(8):4966–4970. doi:https://doi.org/10.1073/pnas.77.8.4966.
- Parker WB, Cheng YC. Metabolism and mechanism of action of 5-fluorouracil. Pharmacol Ther. 1990;48(3):381–395. doi:https://doi.org/10.1016/0163-7258(90)90056-8.
- Aschele C, Sobrero A, Faderan MA, Bertino JR. Novel mechanism (s) of resistance to 5-fluorouracil in human colon cancer (HCT-8) sublines following exposure to two different clinically relevant dose schedules. Cancer Res. 1992;52(7):1855–1864.
- Milano G, McLeod H. Can dihydropyrimidine dehydrogenase impact 5-fluorouracil-based treatment? Eur J Cancer. 2000;36(1):37–42. doi:https://doi.org/10.1016/S0959-8049(99)00211-7.
- Heggie GD, Sommadossi J-P, Cross DS, Huster WJ, Diasio RB. Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine, and bile. Cancer Res. 1987;47(8):2203–2206.
- Saif MW, Syrigos KN, Katirtzoglou NA. S-1: a promising new oral fluoropyrimidine derivative. Expert Opin Investig Drugs. 2009;18(3):335–348. doi:https://doi.org/10.1517/13543780902729412.
- Fraile RJ, Baker LH, Buroker TR, Horwitz J, Vaitkevicius V. Pharmacokinetics of 5-fluorouracil administered orally, by rapid intravenous and by slow infusion. Cancer Res. 1980;40(7):2223–2228.
- Daher GC, Harris BE, Willard EM, Diasio RB. Biochemical basis for circadian-dependent metabolism of fluoropyrimidines. Ann NY Acad Sci. 1991;618:350–361. doi:https://doi.org/10.1111/j.1749-6632.1991.tb27255.x.
- Lamont EB, Schilsky RL. The oral fluoropyrimidines in cancer chemotherapy. Clin Cancer Res. 1999;5(9):2289–2296.
- Harris BE, Carpenter JT, Diasio RB. Severe 5‐fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common pharmacogenetic syndrome. Cancer. 1991;68(3):499–501. doi:https://doi.org/10.1002/1097-0142(19910801)68:3<499::AID-CNCR2820680309>3.0.CO;2-F.
- Lu Z, Zhang R, Diasio RB. Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics, newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy. Cancer Res. 1993;53(22):5433–5438.
- Okuda H, Nishiyama T, Ogura K, Nagayama S, Ikeda K, Yamaguchi S, et al. Lethal drug interactions of sorivudine, a new antiviral drug, with oral 5-fluorouracil prodrugs. Drug Metab Dispos. 1997;25(5):270–273.
- Réti A, Pap É, Adleff V, Jeney A, Kralovánszky J, Budai B. Enhanced 5-fluorouracil cytotoxicity in high cyclooxygenase-2 expressing colorectal cancer cells and xenografts induced by non-steroidal anti-inflammatory drugs via downregulation of dihydropyrimidine dehydrogenase. Cancer Chemother Pharmacol. 2010;66(2):219–227. doi:https://doi.org/10.1007/s00280-009-1149-8.
- Costi MP, Ferrari S, Venturelli A, Calo S, Tondi D, Barlocco D. Thymidylate synthase structure, function and implication in drug discovery. Curr Med Chem. 2005;12(19):2241–2258. doi:https://doi.org/10.2174/0929867054864868.
- Salonga D, Danenberg KD, Johnson M, Metzger R, Groshen S, Tsao-Wei DD, et al. Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase, and thymidine phosphorylase. Clin Cancer Res. 2000;6(4):1322–1327.
- Leichman CG, Lenz H-J, Leichman L, Danenberg K, Baranda J, Groshen S, et al. Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluorouracil and weekly leucovorin. JCO. 1997;15(10):3223–3229. doi:https://doi.org/10.1200/JCO.1997.15.10.3223.
- Aschele C, Debernardis D, Casazza S, Antonelli G, Tunesi G, Baldo C, et al. Immunohistochemical quantitation of thymidylate synthase expression in colorectal cancer metastases predicts for clinical outcome to fluorouracil-based chemotherapy. J Clin Oncol. 1999;17(6):1760–1770. doi:https://doi.org/10.1200/JCO.1999.17.6.1760.
- Gonen M, Hummer A, Zervoudakis A, Sullivan D, Fong Y, Banerjee D, et al. Thymidylate synthase expression in hepatic tumors is a predictor of survival and progression in patients with resectable metastatic colorectal cancer. JCO. 2003;21(3):406–412. doi:https://doi.org/10.1200/JCO.2003.06.060.
- Lurje G, Zhang W, Yang D, Groshen S, Hendifar AE, Husain H, et al. Thymidylate synthase haplotype is associated with tumor recurrence in stage II and stage III colon cancer. Pharmacogenet Genomics. 2008;18(2):161–168. doi:https://doi.org/10.1097/FPC.0b013e3282f4aea6.
- Scott J, Weir D. Folate/vitamin B12 inter-relationships. Essays Biochem. 1994;28:63–72.
- Mouse H. Methylenetetrahydrofolate reductase. Databases. 2001;9028:69–77.
- Sohn K-J, Croxford R, Yates Z, Lucock M, Kim Y-I. Effect of the methylenetetrahydrofolate reductase C677T polymorphism on chemosensitivity of colon and breast cancer cells to 5-fluorouracil and methotrexate. J Natl Cancer Inst. 2004;96(2):134–144. doi:https://doi.org/10.1093/jnci/djh015.
- Vaclavicek A, Bermejo JL, Schmutzler RK, Sutter C, Wappenschmidt B, Meindl A, et al. Polymorphisms in the Janus kinase 2 (JAK)/signal transducer and activator of transcription (STAT) genes: putative association of the STAT gene region with familial breast cancer. Endocr Relat Cancer. 2007;14(2):267–277. doi:https://doi.org/10.1677/ERC-06-0077.
- Calò V, Migliavacca M, Bazan V, Macaluso M, Buscemi M, Gebbia N, et al. STAT proteins: from normal control of cellular events to tumorigenesis. J Cell Physiol. 2003;197(2):157–168. doi:https://doi.org/10.1002/jcp.10364.
- Murray PJ. The JAK-STAT signaling pathway: input and output integration. J Immunol. 2007;178(5):2623–2629. doi:https://doi.org/10.4049/jimmunol.178.5.2623.
- Kisseleva T, Bhattacharya S, Braunstein J, Schindler C. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene. 2002;285(1–2):1–24. doi:https://doi.org/10.1016/S0378-1119(02)00398-0.
- Bromberg J. Stat proteins and oncogenesis. J Clin Invest. 2002;109(9):1139–42. doi:https://doi.org/10.1172/JCI0215617.
- Spitzner M, Roesler B, Bielfeld C, Emons G, Gaedcke J, Wolff HA, et al. STAT3 inhibition sensitizes colorectal cancer to chemoradiotherapy in vitro and in vivo. Int J Cancer. 2014;134(4):997–1007. doi:https://doi.org/10.1002/ijc.28429.
- Darnell JE. Validating Stat3 in cancer therapy. Nat Med. 2005;11(6):595–596. doi:https://doi.org/10.1038/nm0605-595.
- Pouya FD, Rasmi Y, Asl ER. Role of neurotransmitters and neuropeptides in breast cancer metastasis. Biochem Moscow Suppl Ser A. 2020;14(2):107–116. doi:https://doi.org/10.1134/S1990747820020142.
- Chung SS, Giehl N, Wu Y, Vadgama JV. STAT3 activation in HER2-overexpressing breast cancer promotes epithelial-mesenchymal transition and cancer stem cell traits. Int J Oncol. 2014;44(2):403–411. doi:https://doi.org/10.3892/ijo.2013.2195.
- Banerjee K, Resat H. Constitutive activation of STAT3 in breast cancer cells: A review. Int J Cancer. 2016;138(11):2570–2578. doi:https://doi.org/10.1002/ijc.29923.
- Chang Q, Bournazou E, Sansone P, Berishaj M, Gao SP, Daly L, et al. The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis. Neoplasia. 2013;15(7):848–IN45. doi:https://doi.org/10.1593/neo.13706.
- Si W, Shen J, Zheng H, Fan W. The role and mechanisms of action of microRNAs in cancer drug resistance. Clin Epigenetics. 2019;11(1):25. doi:https://doi.org/10.1186/s13148-018-0587-8.
- Zhang F, Wang Z, Fan Y, Xu Q, Ji W, Tian R, et al. Elevated STAT3 signaling-mediated upregulation of MMP-2/9 confers enhanced invasion ability in multidrug-resistant breast cancer cells. Int J Mol Sci. 2015;16(10):24772–24790. doi:https://doi.org/10.3390/ijms161024772.
- Uluer ET, Aydemir I, Inan S, Ozbilgin K, Vatansever HS. Effects of 5-fluorouracil and gemcitabine on a breast cancer cell line (MCF-7) via the JAK/STAT pathway. Acta Histochem. 2012;114(7):641–646. doi:https://doi.org/10.1016/j.acthis.2011.11.010.
- Ma X-T, Wang S, Ye Y-J, Du R-Y, Cui Z-R, Somsouk M. Constitutive activation of Stat3 signaling pathway in human colorectal carcinoma. WJG. 2004;10(11):1569. doi:https://doi.org/10.3748/wjg.v10.i11.1569.
- Corvinus FM, Orth C, Moriggl R, Tsareva SA, Wagner S, Pfitzner EB, et al. Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth. Neoplasia. 2005;7(6):545–555. doi:https://doi.org/10.1593/neo.04571.
- Oh W, Lee E-W, Sung YH, Yang M-R, Ghim J, Lee H-W, et al. Jab1 induces the cytoplasmic localization and degradation of p53 in coordination with Hdm2. J Biol Chem. 2006;281(25):17457–17465. doi:https://doi.org/10.1074/jbc.M601857200.
- Zhang XC, Chen J, Su CH, Yang HY, Lee MH. Roles for CSN5 in control of p53/MDM2 activities. J Cell Biochem. 2008;103(4):1219–1230. doi:https://doi.org/10.1002/jcb.21504.
- Kim B-C, Lee H-J, Park SH, Lee SR, Karpova TS, McNally JG, et al. Jab1/CSN5, a component of the COP9 signalosome, regulates transforming growth factor beta signaling by binding to Smad7 and promoting its degradation. Mol Cell Biol. 2004;24(6):2251–2262. doi:https://doi.org/10.1128/MCB.24.6.2251-2262.2004.
- Kim JH, Choi JK, Cinghu S, Jang JW, Lee YS, Li YH, et al. Jab1/CSN5 induces the cytoplasmic localization and degradation of RUNX3. J Cell Biochem. 2009;107(3):557–565. doi:https://doi.org/10.1002/jcb.22157.
- Tomoda K, Kubota Y, Arata Y, Mori S, Maeda M, Tanaka T, et al. The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex. J Biol Chem. 2002;277(3):2302–2310. doi:https://doi.org/10.1074/jbc.M104431200.
- Kugimiya N, Nishimoto A, Hosoyama T, Ueno K, Takemoto Y, Harada E, et al. JAB1-STAT3 activation loop is associated with recurrence following 5-fluorouracil-based adjuvant chemotherapy in human colorectal cancer. Oncol Lett. 2017;14(5):6203–6209.
- Piscione M, Mazzone M, Di Marcantonio MC, Muraro R, Mincione G. Eradication of Helicobacter pylori and gastric cancer: a controversial relationship. Front Microbiol. 2021;12:630852.
- Wang Z, Si X, Xu A, Meng X, Gao S, Qi Y, et al. Activation of STAT3 in human gastric cancer cells via interleukin (IL)-6-type cytokine signaling correlates with clinical implications. PLoS One. 2013;8(10):e75788. doi:https://doi.org/10.1371/journal.pone.0075788.
- Giraud AS, Menheniott TR, Judd LM. Targeting STAT3 in gastric cancer. Expert Opin Ther Targets. 2012;16(9):889–901. doi:https://doi.org/10.1517/14728222.2012.709238.
- Kanda N, Seno H, Konda Y, Marusawa H, Kanai M, Nakajima T, et al. STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene. 2004;23(28):4921–4929. doi:https://doi.org/10.1038/sj.onc.1207606.
- Gong W, Wang L, Yao JC, Ajani JA, Wei D, Aldape KD, et al. Expression of activated signal transducer and activator of transcription 3 predicts expression of vascular endothelial growth factor in and angiogenic phenotype of human gastric cancer. Clin Cancer Res. 2005;11(4):1386–1393. doi:https://doi.org/10.1158/1078-0432.CCR-04-0487.
- Jackson C, Judd LM, Menheniott T, Kronborg I, Dow C, Yeomans ND, et al. Augmented gp130-mediated cytokine signalling accompanies human gastric cancer progression. J Pathol. 2007;213(2):140–151. doi:https://doi.org/10.1002/path.2218.
- Xu G-y, Tang X-j. Troxerutin (TXN) potentiated 5-fluorouracil (5-Fu) treatment of human gastric cancer through suppressing STAT3/NF-κB and Bcl-2 signaling pathways. Biomed Pharmacother. 2017;92:95–107. doi:https://doi.org/10.1016/j.biopha.2017.04.059.
- Pandey A, Vishnoi K, Mahata S, Tripathi SC, Misra SP, Misra V, et al. Berberine and curcumin target survivin and STAT3 in gastric cancer cells and synergize actions of standard chemotherapeutic 5-fluorouracil. Nutr Cancer. 2015;67(8):1295–1306. doi:https://doi.org/10.1080/01635581.2015.1085581.
- El–Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–2576. doi:https://doi.org/10.1053/j.gastro.2007.04.061.
- Thomas M. Molecular targeted therapy for hepatocellular carcinoma. J Gastroenterol. 2009;44(S19):136–141. doi:https://doi.org/10.1007/s00535-008-2252-z.
- Tang JJH, Thng DKH, Lim JJ, Toh TB. JAK/STAT signaling in hepatocellular carcinoma. Hepat Oncol. 2020;7(1):HEP18.
- Deng L, Ren Z, Jia Q, Wu W, Shen H, Wang Y. Schedule-dependent antitumor effects of 5-fluorouracil combined with sorafenib in hepatocellular carcinoma. BMC Cancer. 2013;13(1):363. doi:https://doi.org/10.1186/1471-2407-13-363.
- Zhang Y, Jia Q-a, Kadel D, Zhang X-f, Zhang Q-b. Targeting mTORC1/2 complexes inhibit tumorigenesis and enhance sensitivity to 5-flourouracil (5-FU) in hepatocellular carcinoma: a preclinical study of mTORC1/2-targeted therapy in hepatocellular carcinoma (HCC). Med Sci Monit. 2018;24:2735–2743. doi:https://doi.org/10.12659/MSM.907514.
- Economopoulou P, de Bree R, Kotsantis I, Psyrri A. Diagnostic tumor markers in head and neck squamous cell carcinoma (HNSCC) in the clinical setting. Front Oncol. 2019;9:827.
- Grandis JR, Drenning SD, Chakraborty A, Zhou MY, Zeng Q, Pitt AS, Tweardy DJ. Requirement of Stat3 but not Stat1 activation for epidermal growth factor receptor- mediated cell growth in vitro. J Clin Invest. 1998;102(7):1385–1392. doi:https://doi.org/10.1172/JCI3785.
- Grandis JR, Drenning SD, Zeng Q, Watkins SC, Melhem MF, Endo S, et al. Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo. Proc Natl Acad Sci USA. 2000;97(8):4227–4232. doi:https://doi.org/10.1073/pnas.97.8.4227.
- Nagpal JK, Mishra R, Das BR. Activation of Stat-3 as one of the early events in tobacco chewing-mediated oral carcinogenesis. Cancer. 2002;94(9):2393–2400. doi:https://doi.org/10.1002/cncr.10499.
- Arredondo J, Chernyavsky AI, Jolkovsky DL, Pinkerton KE, Grando SA. Receptor‐mediated tobacco toxicity: cooperation of the Ras/Raf‐1/MEK1/ERK and JAK‐2/STAT‐3 pathways downstream of a7 nicotinic receptor in oral keratinocytes. FASEB J. 2006;20(12):2093–2101. doi:https://doi.org/10.1096/fj.06-6191com.
- Masuda M, Toh S, Koike K, Kuratomi Y, Suzui M, Deguchi A, et al. The roles of JNK1 and Stat3 in the response of head and neck cancer cell lines to combined treatment with all-trans-retinoic acid and 5-fluorouracil. Jpn J Cancer Res. 2002;93(3):329–339. doi:https://doi.org/10.1111/j.1349-7006.2002.tb02176.x.
- Parkin DM, Bray F. The burden of HPV-related cancers. Vaccine. 2006;24:S11–S25. doi:https://doi.org/10.1016/j.vaccine.2006.05.111.
- Koch M, Wiese M. Gene expression signatures of angiocidin and darapladib treatment connect to therapy options in cervical cancer. J Cancer Res Clin Oncol. 2013;139(2):259–267. doi:https://doi.org/10.1007/s00432-012-1317-9.
- Gutiérrez-Hoya A, Soto-Cruz I. Role of the JAK/STAT pathway in cervical cancer: its relationship with HPV E6/E7 oncoproteins. Cells. 2020;9(10):2297. doi:https://doi.org/10.3390/cells9102297.
- Keane MM, Lowrey GA, Ettenberg SA, Dayton MA, Lipkowitz S. The protein tyrosine phosphatase DEP-1 is induced during differentiation and inhibits growth of breast cancer cells. Cancer Res. 1996;56(18):4236–4243.
- Massa A, Barbieri F, Aiello C, Arena S, Pattarozzi A, Pirani P, et al. The expression of the phosphotyrosine phosphatase DEP-1/PTPeta dictates the responsivity of glioma cells to somatostatin inhibition of cell proliferation. J Biol Chem. 2004;279(28):29004–29012. doi:https://doi.org/10.1074/jbc.M403573200.
- Yan C-M, Zhao Y-L, Cai H-Y, Miao G-Y, Ma W. Blockage of PTPRJ promotes cell growth and resistance to 5-FU through activation of JAK1/STAT3 in the cervical carcinoma cell line C33A. Oncol Rep. 2015;33(4):1737–1744. doi:https://doi.org/10.3892/or.2015.3769.
- Moffat GT, Epstein AS, O'Reilly EM. Pancreatic cancer-A disease in need: optimizing and integrating supportive care. Cancer. 2019;125(22):3927–3935. doi:https://doi.org/10.1002/cncr.32423.
- Ferrand A, Kowalski-Chauvel A, Bertrand C, Escrieut C, Mathieu A, Portolan G, et al. A novel mechanism for JAK2 activation by a G protein-coupled receptor, the CCK2R: implication of this signaling pathway in pancreatic tumor models. J Biol Chem. 2005;280(11):10710–10715. doi:https://doi.org/10.1074/jbc.M413309200.
- Wei D, Le X, Zheng L, Wang L, Frey JA, Gao AC, et al. Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis. Oncogene. 2003;22(3):319–329. doi:https://doi.org/10.1038/sj.onc.1206122.
- Scholz A, Heinze S, Detjen KM, Peters M, Welzel M, Hauff P, et al. Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology. 2003;125(3):891–905. doi:https://doi.org/10.1016/s0016-5085(03)01064-3.
- Elander N, Aughton K, Ghaneh P, Neoptolemos J, Palmer D, Cox T, et al. Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer. Br J Cancer. 2018;118(7):947–954. doi:https://doi.org/10.1038/s41416-018-0004-2.
- Murakawa M, Aoyama T, Miyagi Y, Atsumi Y, Kazama K, Yamaoku K, et al. Clinical implications of dihydropyrimidine dehydrogenase expression in patients with pancreatic cancer who undergo curative resection with S-1 adjuvant chemotherapy. Oncol Lett. 2017;14(2):1505–1511. doi:https://doi.org/10.3892/ol.2017.6295.
- Milano G, Fischel J-L, Etienne M-C, Renée N, Formento P, Thyss A, et al. Inhibition of dihydropyrimidine dehydrogenase by alpha-interferon: experimental data on human tumor cell lines. Cancer Chemother Pharmacol. 1994;34(2):147–152. doi:https://doi.org/10.1007/BF00685932.
- Yuan J, Zhang F, Niu R. Multiple regulation pathways and pivotal biological functions of STAT3 in cancer. Sci Rep. 2015;5(1):1–10.
- Dreesen O, Brivanlou AH. Signaling pathways in cancer and embryonic stem cells. Stem Cell Rev. 2007;3(1):7–17. doi:https://doi.org/10.1007/s12015-007-0004-8.
- Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810. doi:https://doi.org/10.1146/annurev.cellbio.20.010403.113126.
- Tetsu O, McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. 1999;398(6726):422–426. doi:https://doi.org/10.1038/18884.
- Axelrod JD. Progress and challenges in understanding planar cell polarity signaling. Semin Cell Dev Biol. 2009;20(8):964–971. editor Elsevier. doi:https://doi.org/10.1016/j.semcdb.2009.08.001.
- Kikuchi A, Yamamoto H, Sato A, Matsumoto S. New insights into the mechanism of Wnt signaling pathway activation. Int Rev Cell Mol Biol. 2011;291:21–71. doi:https://doi.org/10.1016/B978-0-12-386035-4.00002-1.
- Niehrs C. The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol. 2012;13(12):767–779. doi:https://doi.org/10.1038/nrm3470.
- De A. Wnt/Ca2+ signaling pathway: a brief overview. Acta Biochim Biophys Sin. 2011;43(10):745–756. doi:https://doi.org/10.1093/abbs/gmr079.
- Nakopoulou L, Mylona E, Papadaki I, Kavantzas N, Giannopoulou I, Markaki S, et al. Study of phospho-beta-catenin subcellular distribution in invasive breast carcinomas in relation to their phenotype and the clinical outcome. Mod Pathol. 2006;19(4):556–563. doi:https://doi.org/10.1038/modpathol.3800562.
- Mohinta S, Wu H, Chaurasia P, Watabe K. Wnt pathway and breast cancer. Front Biosci. 2007;12(2):4020–4033. doi:https://doi.org/10.2741/2368.
- Huang C, Chen Y, Liu H, Yang J, Song X, Zhao J, et al. Celecoxib targets breast cancer stem cells by inhibiting the synthesis of prostaglandin E2 and down-regulating the Wnt pathway activity. Oncotarget. 2017;8(70):115254–115269. doi:https://doi.org/10.18632/oncotarget.23250.
- Potten CS, Morris RJ. Epithelial stem cells in vivo. J Cell Sci Suppl. 1988;10 (Supplement 10):45–62. doi:https://doi.org/10.1242/jcs.1988.supplement_10.4.
- Kuhnert F, Davis CR, Wang H-T, Chu P, Lee M, Yuan J, et al. Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1. Proc Natl Acad Sci U S A. 2004;101(1):266–271. doi:https://doi.org/10.1073/pnas.2536800100.
- Korinek V, Barker N, Moerer P, van Donselaar E, Huls G, Peters PJ, et al. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet. 1998;19(4):379–383. doi:https://doi.org/10.1038/1270.
- van Es JH, Haegebarth A, Kujala P, Itzkovitz S, Koo B-K, Boj SF, et al. A critical role for the Wnt effector Tcf4 in adult intestinal homeostatic self-renewal. Mol Cell Biol. 2012;32(10):1918–1927. doi:https://doi.org/10.1128/MCB.06288-11.
- Network CGA. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330.
- Suraweera N, Robinson J, Volikos E, Guenther T, Talbot I, Tomlinson I, et al. Mutations within Wnt pathway genes in sporadic colorectal cancers and cell lines. Int J Cancer. 2006;119(8):1837–1842. doi:https://doi.org/10.1002/ijc.22046.
- Kitaeva MN, Grogan L, Williams JP, Dimond E, Nakahara K, Hausner P, et al. Mutations in β-catenin are uncommon in colorectal cancer occurring in occasional replication error-positive tumors. Cancer Res. 1997;57(20):4478–4481.
- Ozturk N, Singh I, Mehta A, Braun T, Barreto G. HMGA proteins as modulators of chromatin structure during transcriptional activation. Front Cell Dev Biol. 2014;2:5.
- Reeves R. Molecular biology of HMGA proteins: hubs of nuclear function. Gene. 2001;277(1–2):63–81. doi:https://doi.org/10.1016/S0378-1119(01)00689-8.
- Fusco A, Fedele M. Roles of HMGA proteins in cancer. Nat Rev Cancer. 2007;7(12):899–910. doi:https://doi.org/10.1038/nrc2271.
- Kishi Y, Fujii Y, Hirabayashi Y, Gotoh Y. HMGA regulates the global chromatin state and neurogenic potential in neocortical precursor cells. Nat Neurosci. 2012;15(8):1127–1133. doi:https://doi.org/10.1038/nn.3165.
- Li Y, Zhang X, Chen D, Ma C. Let-7a suppresses glioma cell proliferation and invasion through TGF-β/Smad3 signaling pathway by targeting HMGA2. Tumour Biol. 2016;37(6):8107–8119. doi:https://doi.org/10.1007/s13277-015-4674-6.
- Tan L, Wei X, Zheng L, Zeng J, Liu H, Yang S, et al. Amplified HMGA2 promotes cell growth by regulating Akt pathway in AML. J Cancer Res Clin Oncol. 2016;142(2):389–399. doi:https://doi.org/10.1007/s00432-015-2036-9.
- Xu X, Wang Y, Deng H, Liu C, Wu J, Lai M. HMGA2 enhances 5-fluorouracil chemoresistance in colorectal cancer via the Dvl2/Wnt pathway. Oncotarget. 2018;9(11):9963–9974. doi:https://doi.org/10.18632/oncotarget.24133.
- He L, Zhu H, Zhou S, Wu T, Wu H, Yang H, et al. Wnt pathway is involved in 5-FU drug resistance of colorectal cancer cells. Exp Mol Med. 2018;50(8):1–12. doi:https://doi.org/10.1038/s12276-018-0128-8.
- Patil M, Pabla N, Dong Z. Checkpoint kinase 1 in DNA damage response and cell cycle regulation. Cell Mol Life Sci. 2013;70(21):4009–4021. doi:https://doi.org/10.1007/s00018-013-1307-3.
- Liu Q, Guntuku S, Cui X-S, Matsuoka S, Cortez D, Tamai K, et al. Chk1 is an essential kinase that is regulated by Atr and required for the G2/M DNA damage checkpoint. Genes Dev. 2000;14(12):1448–1459. doi:https://doi.org/10.1101/gad.14.12.1448.
- Stracker TH, Usui T, Petrini JH. Taking the time to make important decisions: the checkpoint effector kinases Chk1 and Chk2 and the DNA damage response. DNA Repair. 2009;8(9):1047–1054. doi:https://doi.org/10.1016/j.dnarep.2009.04.012.
- Sørensen CS, Syljuåsen RG. Safeguarding genome integrity: the checkpoint kinases ATR, CHK1 and WEE1 restrain CDK activity during normal DNA replication. Nucleic Acids Res. 2012;40(2):477–486.
- Mak JP, Man WY, Ma HT, Poon RY. Pharmacological targeting the ATR-CHK1-WEE1 axis involves balancing cell growth stimulation and apoptosis. Oncotarget. 2014;5(21):10546–10557. doi:https://doi.org/10.18632/oncotarget.2508.
- Zhang Y, Hunter T. Roles of Chk1 in cell biology and cancer therapy. Int J Cancer. 2014;134(5):1013–1023. doi:https://doi.org/10.1002/ijc.28226.
- Tapia-Alveal C, Calonge TM, O'Connell MJ. Regulation of chk1. Cell Div. 2009;4(1):8. doi:https://doi.org/10.1186/1747-1028-4-8.
- Milczarek M, Rossowska J, Klopotowska D, Stachowicz M, Kutner A, Wietrzyk J. Tacalcitol increases the sensitivity of colorectal cancer cells to 5-fluorouracil by downregulating the thymidylate synthase. J Steroid Biochem Mol Biol. 2019;190:139–151. doi:https://doi.org/10.1016/j.jsbmb.2019.03.017.
- Moon CM, Kwon JH, Kim JS, Oh SH, Jin Lee K, Park JJ, et al. Nonsteroidal anti-inflammatory drugs suppress cancer stem cells via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal cancer. Int J Cancer. 2014;134(3):519–529. doi:https://doi.org/10.1002/ijc.28381.
- Jalilvand A, Soltanpour MS. Investigating the methylation status of DACT2 gene and its association with MTHFR C677T polymorphism in patients with colorectal cancer. Mol Biol Res Commun. 2019;8(2):53.
- Jalilvand A, Soltanpour MS. Promoter hypermethylation of Wnt/β-catenin signaling pathway inhibitor WIF-1 gene and its association with MTHFR C677T polymorphism in patients with colorectal cancer. Oman Med J. 2020;35(3):e131–e131. doi:https://doi.org/10.5001/omj.2020.49.
- Talbot LJ, Bhattacharya SD, Kuo PC. Epithelial-mesenchymal transition, the tumor microenvironment, and metastatic behavior of epithelial malignancies. Int J Biochem Mol Biol. 2012;3(2):117–136.
- Chiurillo MA. Role of the Wnt/β-catenin pathway in gastric cancer: an in-depth literature review. World J Exp Med. 2015;5(2):84–102. doi:https://doi.org/10.5493/wjem.v5.i2.84.
- Gonçalves LM, Valente IM, Rodrigues JA. An overview on cardamonin. J Med Food. 2014;17(6):633–640. doi:https://doi.org/10.1089/jmf.2013.0061.
- Li Y, Qin Y, Yang C, Zhang H, Li Y, Wu B, et al. Cardamonin induces ROS-mediated G2/M phase arrest and apoptosis through inhibition of NF-κB pathway in nasopharyngeal carcinoma. Cell Death Dis. 2017;8(8):e3024. doi:https://doi.org/10.1038/cddis.2017.407.
- Zhang J, Sikka S, Siveen KS, Lee JH, Um J-Y, Kumar AP, et al. Cardamonin represses proliferation, invasion, and causes apoptosis through the modulation of signal transducer and activator of transcription 3 pathway in prostate cancer. Apoptosis. 2017;22(1):158–168. doi:https://doi.org/10.1007/s10495-016-1313-7.
- Wu N, Liu J, Zhao X, Yan Z, Jiang B, Wang L, et al. Cardamonin induces apoptosis by suppressing STAT3 signaling pathway in glioblastoma stem cells. Tumour Biol. 2015;36(12):9667–9676. doi:https://doi.org/10.1007/s13277-015-3673-y.
- Niu P, Shi D, Zhang S, Zhu Y, Zhou J. Cardamonin enhances the anti-proliferative effect of cisplatin on ovarian cancer. Oncol Lett. 2018;15(3):3991–3997. doi:https://doi.org/10.3892/ol.2018.7743.
- Hou G, Yuan X, Li Y, Hou G, Liu X. Cardamonin, a natural chalcone, reduces 5-fluorouracil resistance of gastric cancer cells through targeting Wnt/β-catenin signal pathway. Invest New Drugs. 2020;38(2):329–411. doi:https://doi.org/10.1007/s10637-019-00781-9.
- Wang B, Guan G, Zhao D. Silence of FAM83H-AS1 promotes chemosensitivity of gastric cancer through Wnt/β-catenin signaling pathway. Biomed Pharmacother. 2020;125:109961. doi:https://doi.org/10.1016/j.biopha.2020.109961.
- Laurent-Puig P, Zucman-Rossi J. Genetics of hepatocellular tumors. Oncogene. 2006;25(27):3778–3786. doi:https://doi.org/10.1038/sj.onc.1209547.
- Breuhahn K, Longerich T, Schirmacher P. Dysregulation of growth factor signaling in human hepatocellular carcinoma. Oncogene. 2006;25(27):3787–3800. doi:https://doi.org/10.1038/sj.onc.1209556.
- Salahshor S, Woodgett J. The links between axin and carcinogenesis. J Clin Pathol. 2005;58(3):225–236. doi:https://doi.org/10.1136/jcp.2003.009506.
- Chiba S. Concise review: Notch signaling in stem cell systems. Stem Cells. 2006;24(11):2437–2447. doi:https://doi.org/10.1634/stemcells.2005-0661.
- Nejak-Bowen KN, Monga SP. Beta-catenin signaling, liver regeneration and hepatocellular cancer: sorting the good from the bad. Semin Cancer Biol. 2011;21(1):44–58.
- Obi S, Yoshida H, Toune R, Unuma T, Kanda M, Sato S, et al. Combination therapy of intraarterial 5-fluorouracil and systemic interferon-alpha for advanced hepatocellular carcinoma with portal venous invasion. Cancer. 2006;106(9):1990–1997. doi:https://doi.org/10.1002/cncr.21832.
- Baron S, Dianzani F. The interferons: a biological system with therapeutic potential in viral infections. Antiviral Res. 1994;24(2–3):97–110. doi:https://doi.org/10.1016/0166-3542(94)90058-2.
- Noda T, Nagano H, Takemasa I, Yoshioka S, Murakami M, Wada H, et al. Activation of Wnt/beta-catenin signalling pathway induces chemoresistance to interferon-alpha/5-fluorouracil combination therapy for hepatocellular carcinoma. Br J Cancer. 2009;100(10):1647–1658. doi:https://doi.org/10.1038/sj.bjc.6605064.
- Xu Y, Zhang C, Liang H, Hu S, Li P, Liu L, et al. Dishevelled 1, a pivotal positive regulator of the Wnt signalling pathway, mediates 5-fluorouracil resistance in HepG2 cells. Artif Cells Nanomed Biotechnol. 2018;46(sup2):192–200. doi:https://doi.org/10.1080/21691401.2018.1453827.
- Wei YL, Hua J, Liu XY, Hua XM, Sun C, Bai JA, et al. LncNEN885 inhibits epithelial-mesenchymal transition by partially regulation of Wnt/β-catenin signalling in gastroenteropancreatic neuroendocrine neoplasms. Cancer Sci. 2018;109(10):3139–3148. doi:https://doi.org/10.1111/cas.13747.
- Frost M, Lines KE, Thakker RV. Current and emerging therapies for PNETs in patients with or without MEN1. Nat Rev Endocrinol. 2018;14(4):216–227. doi:https://doi.org/10.1038/nrendo.2018.3.
- Jiang X, Cao Y, Li F, Su Y, Li Y, Peng Y, et al. Targeting β-catenin signaling for therapeutic intervention in MEN1-deficient pancreatic neuroendocrine tumours. Nat Commun. 2014;5(1):1–13. doi:https://doi.org/10.1038/ncomms6809.
- Lines K, Stevenson M, Filippakopoulos P, Müller S, Lockstone H, Wright B, et al. Epigenetic pathway inhibitors represent potential drugs for treating pancreatic and bronchial neuroendocrine tumors. Oncogenesis. 2017;6(5):e332–e. doi:https://doi.org/10.1038/oncsis.2017.30.
- Simbolo M, Barbi S, Fassan M, Mafficini A, Ali G, Vicentini C, et al. Gene expression profiling of lung atypical carcinoids and large cell neuroendocrine carcinomas identifies three transcriptomic subtypes with specific genomic alterations. J Thorac Oncol. 2019;14(9):1651–1661. doi:https://doi.org/10.1016/j.jtho.2019.05.003.
- Veschi S, Lattanzio R, Aceto GM, Curia MC, Magnasco S, Angelucci D, et al. Alterations of MEN1 and E-cadherin/β-catenin complex in sporadic pulmonary carcinoids. Int J Oncol Res. 2012;41(4):1221–1228.
- Scarpa A, Chang DK, Nones K, Corbo V, Patch A-M, Bailey P, et al. Whole-genome landscape of pancreatic neuroendocrine tumours. Nature. 2017;543(7643):65–71. doi:https://doi.org/10.1038/nature21063.
- Jin X-F, Spöttl G, Maurer J, Nölting S, Auernhammer CJ. Inhibition of Wnt/β-catenin signaling in neuroendocrine tumors in vitro: antitumoral effects. Cancers. 2020;12(2):345. doi:https://doi.org/10.3390/cancers12020345.
- Prada ETA, Weis C, Orth M, Lauseker M, Spöttl G, Maurer J, et al. GSK3α/β: a novel therapeutic target for neuroendocrine tumors. Neuroendocrinology. 2018;106(4):335–351. doi:https://doi.org/10.1159/000481887.
- Miele L. Notch signaling. Clin Cancer Res. 2006;12(4):1074–1079. doi:https://doi.org/10.1158/1078-0432.CCR-05-2570.
- Miele L, Osborne B. Arbiter of differentiation and death: Notch signaling meets apoptosis. J Cell Phys. 1999;181(3):393–409. doi:https://doi.org/10.1002/(SICI)1097-4652(199912)181:3<393::AID-JCP3>3.0.CO;2-6.
- Yuan X, Wu H, Xu H, Xiong H, Chu Q, Yu S, et al. Notch signaling: an emerging therapeutic target for cancer treatment. Cancer Lett. 2015;369(1):20–27. doi:https://doi.org/10.1016/j.canlet.2015.07.048.
- Li DD, Zhao CH, Ding HW, Wu Q, Ren TS, Wang J, et al. A novel inhibitor of ADAM17 sensitizes colorectal cancer cells to 5-fluorouracil by reversing Notch and epithelial-mesenchymal transition in vitro and in vivo. Cell Prolif. 2018;51(5):e12480. doi:https://doi.org/10.1111/cpr.12480.
- Zhang X, Chen T, Zhang J, Mao Q, Li S, Xiong W, et al. Notch1 promotes glioma cell migration and invasion by stimulating β-catenin and NF-κB signaling via AKT activation. Cancer Sci. 2012;103(2):181–190. doi:https://doi.org/10.1111/j.1349-7006.2011.02154.x.
- Garcia A, Kandel JJ. Notch: a key regulator of tumor angiogenesis and metastasis. Histol Histopathol. 2012;27(2):151–156.
- Shaik JP, Alanazi IO, Pathan AAK, Parine NR, Almadi MA, Azzam NA, et al. Frequent activation of Notch signaling pathway in colorectal cancers and its implication in patient survival outcome. J Oncol. 2020;2020:1–8. doi:https://doi.org/10.1155/2020/6768942.
- Liu H, Yin Y, Hu Y, Feng Y, Bian Z, Yao S, et al. miR-139-5p sensitizes colorectal cancer cells to 5-fluorouracil by targeting NOTCH-1. Pathol Res Pract. 2016;212(7):643–649. doi:https://doi.org/10.1016/j.prp.2016.04.011.
- Candy P, Phillips M, Redfern AD, Colley SM, Davidson J, Stuart LM, et al. Notch-induced transcription factors are predictive of survival and 5-fluorouracil response in colorectal cancer patients. Br J Cancer. 2013;109(4):1023–1030. doi:https://doi.org/10.1038/bjc.2013.431.
- Guglielmi A, Ruzzenente A, Campagnaro T, Pachera S, Valdegamberi A, Nicoli P, et al. Intrahepatic cholangiocarcinoma: prognostic factors after surgical resection. World J Surg. 2009;33(6):1247–1254. doi:https://doi.org/10.1007/s00268-009-9970-0.
- Xue T-C, Zhang B-H, Ye S-L, Ren Z-G. Differentially expressed gene profiles of intrahepatic cholangiocarcinoma, hepatocellular carcinoma, and combined hepatocellular-cholangiocarcinoma by integrated microarray analysis. Tumour Biol. 2015;36(8):5891–5899. doi:https://doi.org/10.1007/s13277-015-3261-1.
- Wu W-R, Shi X-D, Zhang R, Zhu M-S, Xu L-B, Yu X-H, et al. Clinicopathological significance of aberrant Notch receptors in intrahepatic cholangiocarcinoma. Int J Clin Exp Pathol. 2014;7(6):3272.
- Wu W-R, Zhang R, Shi X-D, Zhu M-S, Xu L-B, Zeng H, et al. Notch1 is overexpressed in human intrahepatic cholangiocarcinoma and is associated with its proliferation, invasiveness and sensitivity to 5-fluorouracil in vitro. Oncol Rep. 2014;31(6):2515–2524. doi:https://doi.org/10.3892/or.2014.3123.
- Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol. 2009;1(4):a000034. doi:https://doi.org/10.1101/cshperspect.a000034.
- Sun S-C, Chang J-H, Jin J. Regulation of nuclear factor-κB in autoimmunity. Trends Immunol. 2013;34(6):282–289. doi:https://doi.org/10.1016/j.it.2013.01.004.
- Sun S-C. Non-canonical NF-κB signaling pathway. Cell Res. 2011;21(1):71–85. doi:https://doi.org/10.1038/cr.2010.177.
- Zhang Q, Lenardo MJ, Baltimore D. 30 years of NF-κB: a blossoming of relevance to human pathobiology. Cell. 2017;168(1–2):37–57. doi:https://doi.org/10.1016/j.cell.2016.12.012.
- Hoesel B, Schmid JA. The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. 2013;12(1):86–15. doi:https://doi.org/10.1186/1476-4598-12-86.
- Lim S-O, Li C-W, Xia W, Cha J-H, Chan L-C, Wu Y, et al. Deubiquitination and stabilization of PD-L1 by CSN5. Cancer Cell. 2016;30(6):925–939. doi:https://doi.org/10.1016/j.ccell.2016.10.010.
- Sun SC. The noncanonical NF-κB pathway. Immunol Rev. 2012;246(1):125–140. doi:https://doi.org/10.1111/j.1600-065X.2011.01088.x.
- Sun S-C. The non-canonical NF-κB pathway in immunity and inflammation. Nat Rev Immunol. 2017;17(9):545–558. doi:https://doi.org/10.1038/nri.2017.52.
- Vaiopoulos AG, Papachroni KK, Papavassiliou AG. Colon carcinogenesis: learning from NF-kappaB and AP-1. Int J Biochem Cell Biol. 2010;42(7):1061–1065. doi:https://doi.org/10.1016/j.biocel.2010.03.018.
- Terzić J, Grivennikov S, Karin E, Karin M. Inflammation and colon cancer. Gastroenterology. 2010;138(6):2101–14.e5. doi:https://doi.org/10.1053/j.gastro.2010.01.058.
- Sunami Y, Wirth T. Intestinal carcinogenesis: IKK can go all the way. J Clin Invest. 2011;121(7):2551–2553. doi:https://doi.org/10.1172/JCI58454.
- Greten FR, Arkan MC, Bollrath J, Hsu L-C, Goode J, Miething C, et al. NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta. Cell. 2007;130(5):918–931. doi:https://doi.org/10.1016/j.cell.2007.07.009.
- Koerber MI, Staribacher A, Ratzenböck I, Steger G, Mader RM. NFκB-associated pathways in progression of chemoresistance to 5-fluorouracil in an in vitro model of colonic carcinoma. Anticancer Res. 2016;36(4):1631–1639.
- Zhao C, Zhao Q, Zhang C, Wang G, Yao Y, Huang X, et al. miR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis. Sci Rep. 2017;7(1):1–12. doi:https://doi.org/10.1038/s41598-017-04172-z.
- Shi D-B, Li X-X, Zheng H-T, Li D-W, Cai G-X, Peng J-J, et al. Icariin-mediated inhibition of NF-κB activity enhances the in vitro and in vivo antitumour effect of 5-fluorouracil in colorectal cancer. Cell Biochem Biophys. 2014;69(3):523–530. doi:https://doi.org/10.1007/s12013-014-9827-5.
- Shakibaei M, Kraehe P, Popper B, Shayan P, Goel A, Buhrmann C. Curcumin potentiates antitumor activity of 5-fluorouracil in a 3D alginate tumor microenvironment of colorectal cancer. BMC Cancer. 2015;15(1):250. doi:https://doi.org/10.1186/s12885-015-1291-0.
- Fu J, Xu Y, Yang Y, Liu Y, Ma L, Zhang Y. Aspirin suppresses chemoresistance and enhances antitumor activity of 5-Fu in 5-Fu-resistant colorectal cancer by abolishing 5-Fu-induced NF-κB activation. Sci Rep. 2019;9(1):1–11. doi:https://doi.org/10.1038/s41598-019-53276-1.
- Wang W, McLeod HL, Cassidy J. Disulfiram-mediated inhibition of NF-kappaB activity enhances cytotoxicity of 5-fluorouracil in human colorectal cancer cell lines. Int J Cancer. 2003;104(4):504–511. doi:https://doi.org/10.1002/ijc.10972.
- Nam S, Ko Y, Jung J, Yoon J, Kim Y, Choi Y, et al. A hypoxia-dependent upregulation of hypoxia-inducible factor-1 by nuclear factor-κ B promotes gastric tumour growth and angiogenesis. Br J Cancer. 2011;104(1):166–174. doi:https://doi.org/10.1038/sj.bjc.6606020.
- Hu Z, Liu X, Tang Z, Zhou Y, Qiao L. Possible regulatory role of snail in NF-κB-mediated changes in E-cadherin in gastric in gastric cancer. Oncol Rep. 2013;29(3):993–1000. doi:https://doi.org/10.3892/or.2012.2200.
- Sokolova O, Naumann M. NF‐κB signaling in gastric cancer. Toxins. 2017;9(4):119. doi:https://doi.org/10.3390/toxins9040119.
- Manu KA, Shanmugam MK, Li F, Chen L, Siveen KS, Ahn KS, et al. Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products. J Mol Med. 2014;92(3):267–276. doi:https://doi.org/10.1007/s00109-013-1095-0.
- Wu H, Li W, Wang T, Shu Y, Liu P. Paeoniflorin suppress NF-kappaB activation through modulation of I kappaB alpha and enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells. Biomed Pharmacother. 2008;62(9):659–666. doi:https://doi.org/10.1016/j.biopha.2008.08.002.
- Wang S, Yao Y, Rao C, Zheng G, Chen W. 25-HC decreases the sensitivity of human gastric cancer cells to 5-fluorouracil and promotes cells invasion via the TLR2/NF-κB signaling pathway. Int J Oncol. 2019;54(3):966–980. doi:https://doi.org/10.3892/ijo.2019.4684.
- Kang Y, Hu W, Bai E, Zheng H, Liu Z, Wu J, et al. Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway. Onco Targets Ther. 2016;9:7373–384. doi:https://doi.org/10.2147/OTT.S118272.
- Gibson MK, Dhaliwal AS, Clemons NJ, Phillips WA, Dvorak K, Tong D, et al. Barrett's esophagus: cancer and molecular biology. Ann N Y Acad Sci. 2013;1300(1):296–314. doi:https://doi.org/10.1111/nyas.12252.
- Kang MR, Kim MS, Kim SS, Ahn CH, Yoo NJ, Lee SH. NF-kappaB signalling proteins p50/p105, p52/p100, RelA, and IKKepsilon are over-expressed in oesophageal squamous cell carcinomas. Pathology. 2009;41(7):622–625. doi:https://doi.org/10.3109/00313020903257756.
- Li B, Li YY, Tsao SW, Cheung AL. Targeting NF-kappaB signaling pathway suppresses tumor growth, angiogenesis, and metastasis of human esophageal cancer. Mol Cancer Ther. 2009;8(9):2635–2644. doi:https://doi.org/10.1158/1535-7163.MCT-09-0162.
- Tian F, Fan T, Zhang Y, Jiang Y, Zhang X. Curcumin potentiates the antitumor effects of 5-FU in treatment of esophageal squamous carcinoma cells through downregulating the activation of NF-κB signaling pathway in vitro and in vivo. Acta Biochim Biophys Sin. 2012;44(10):847–855. doi:https://doi.org/10.1093/abbs/gms074.
- Zhang H, Ozaki I, Hamajima H, Iwane S, Takahashi H, Kawaguchi Y, et al. Vitamin K2 augments 5-fluorouracil-induced growth inhibition of human hepatocellular carcinoma cells by inhibiting NF-κB activation. Oncol Rep. 2011;25(1):159–166.
- Zhu W-P, Liu Z-Y, Zhao Y-M, He X-G, Pan Q, Zhang N, et al. Dihydropyrimidine dehydrogenase predicts survival and response to interferon-α in hepatocellular carcinoma. Cell Death Dis. 2018;9(2):1–13. doi:https://doi.org/10.1038/s41419-017-0098-0.
- di Magliano MP, Hebrok M. Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer. 2003;3(12):903–911. doi:https://doi.org/10.1038/nrc1229.
- Ingham PW, McMahon AP. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 2001;15(23):3059–3087. doi:https://doi.org/10.1101/gad.938601.
- Alcedo J, Ayzenzon M, Von Ohlen T, Noll M, Hooper JE. The Drosophila smoothened gene encodes a seven-pass membrane protein, a putative receptor for the hedgehog signal. Cell. 1996;86(2):221–32. doi:https://doi.org/10.1016/s0092-8674(00)80094-x.
- Rubin LL, de Sauvage FJ. Targeting the Hedgehog pathway in cancer. Nat Rev Drug Discov. 2006;5(12):1026–1033. doi:https://doi.org/10.1038/nrd2086.
- Van Den Brink GR, Bleuming SA, Hardwick JC, Schepman BL, Offerhaus GJ, Keller JJ, et al. Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation. Nat Genet. 2004;36(3):277–282. doi:https://doi.org/10.1038/ng1304.
- Shi T, Mazumdar T, DeVecchio J, Duan Z-H, Agyeman A, Aziz M, et al. cDNA microarray gene expression profiling of hedgehog signaling pathway inhibition in human colon cancer cells. PLoS One. 2010;5(10):e13054. doi:https://doi.org/10.1371/journal.pone.0013054.
- Taniguchi H, Yamamoto H, Akutsu N, Nosho K, Adachi Y, Imai K, et al. Transcriptional silencing of hedgehog-interacting protein by CpG hypermethylation and chromatic structure in human gastrointestinal cancer. J Pathol. 2007;213(2):131–139. doi:https://doi.org/10.1002/path.2216.
- You S, Zhou J, Chen S, Zhou P, Lv J, Han X, et al. PTCH1, a receptor of Hedgehog signaling pathway, is correlated with metastatic potential of colorectal cancer. Ups J Med Sci. 2010;115(3):169–175. doi:https://doi.org/10.3109/03009731003668316.
- Varnat F, Duquet A, Malerba M, Zbinden M, Mas C, Gervaz P, et al. Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med. 2009;1(6–7):338–351. doi:https://doi.org/10.1002/emmm.200900039.
- Cai X, Yu K, Zhang L, Li Y, Li Q, Yang Z, et al. Synergistic inhibition of colon carcinoma cell growth by Hedgehog-Gli1 inhibitor arsenic trioxide and phosphoinositide 3-kinase inhibitor LY294002. Onco Targets Ther. 2015;8:877–883.
- Mazumdar T, DeVecchio J, Agyeman A, Shi T, Houghton JA. The GLI genes as the molecular switch in disrupting Hedgehog signaling in colon cancer. Oncotarget. 2011;2(8):638–645. doi:https://doi.org/10.18632/oncotarget.310.
- Agyeman A, Mazumdar T, Houghton JA. Regulation of DNA damage following termination of Hedgehog (HH) survival signaling at the level of the GLI genes in human colon cancer. Oncotarget. 2012;3(8):854–868. doi:https://doi.org/10.18632/oncotarget.586.
- Wu C, Zhu X, Liu W, Ruan T, Tao K. Hedgehog signaling pathway in colorectal cancer: function, mechanism, and therapy. Onco Targets Ther. 2017;10:3249–3259. doi:https://doi.org/10.2147/OTT.S139639.
- Liu Y, Du F, Zhao Q, Jin J, Ma X, Li H. Acquisition of 5-fluorouracil resistance induces epithelial-mesenchymal transitions through the Hedgehog signaling pathway in HCT-8 colon cancer cells. Oncol Lett. 2015;9(6):2675–2679. doi:https://doi.org/10.3892/ol.2015.3136.
- McMahon AP, Ingham PW, Tabin CJ. Developmental roles and clinical significance of Hedgehog signaling. Curr Top Dev Biol. 2003;53:1–114.
- Sicklick JK, Li Y-X, Jayaraman A, Kannangai R, Qi Y, Vivekanandan P, et al. Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis. Carcinogenesis. 2006;27(4):748–757. doi:https://doi.org/10.1093/carcin/bgi292.
- Wang Q, Huang S, Yang L, Zhao L, Yin Y, Liu Z, et al. Down‐regulation of Sonic hedgehog signaling pathway activity is involved in 5‐fluorouracil‐induced apoptosis and motility inhibition in Hep3B cells. Acta Biochim Biophys Sin. 2008;40(9):819–829.