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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 潘敏雄 | zh_TW |
| dc.contributor.advisor | Min-Hsiung Pan | en |
| dc.contributor.author | 何品諭 | zh_TW |
| dc.contributor.author | Pin-Yu Ho | en |
| dc.date.accessioned | 2026-02-11T16:39:37Z | - |
| dc.date.available | 2026-02-12 | - |
| dc.date.copyright | 2026-02-11 | - |
| dc.date.issued | 2026 | - |
| dc.date.submitted | 2026-02-03 | - |
| dc.identifier.citation | Abdel-Shafy, H. I., & Mansour, M. S. (2016). A review on polycyclic aromatic hydrocarbons: source, environmental impact, effect on human health and remediation. Egyptian Journal of Petroleum, 25(1), 107-123.
Adebayo, A. S., Agbaje, K., Adesina, S. K., & Olajubutu, O. (2023). Colorectal cancer: disease process, current treatment options, and future perspectives. Pharmaceutics, 15(11), 2620. Agus A., D. J., Thévenot J., Martinez-Medina M., Massier S., Sauvanet P., Bernalier-Donadille A., Denis S., Hofman P., Bonnet R., Billard E., Barnich N. (2016). Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation. Scientific Reports, 6(1), 19032. Alas, S., & Bonavida, B. (2003). Inhibition of constitutive STAT3 activity sensitizes resistant non-Hodgkin’s lymphoma and multiple myeloma to chemotherapeutic drug-mediated apoptosis. Clinical cancer research, 9(1), 316-326. Alzahrani, S. M., Al Doghaither, H. A., & Al‑Ghafari, A. B. (2021). General insight into cancer: An overview of colorectal cancer. Molecular and Clinical Oncology, 15(6), 1-8. Arlt, V. M., Stiborova, M., Henderson, C. J., Thiemann, M., Frei, E., Aimova, D., Singh, R., Gamboa da Costa, G., Schmitz, O. J., & Farmer, P. B. (2008). Metabolic activation of benzo [a] pyrene in vitro by hepatic cytochrome P450 contrasts with detoxification in vivo: experiments with hepatic cytochrome P450 reductase null mice. Carcinogenesis, 29(3), 656-665. Armitage, P., & Doll, R. (2004). The age distribution of cancer and a multi-stage theory of carcinogenesis. British Journal of Cancer, 91(12), 1983-1989. Auteri, M., Zizzo, M. G., & Serio, R. (2015). GABA and GABA receptors in the gastrointestinal tract: from motility to inflammation. Pharmacological Research, 93, 11-21. Authority, E. F. S. (2008). Polycyclic aromatic hydrocarbons in food‐scientific opinion of the panel on contaminants in the food chain. EFSA journal, 6(8), 724. Bürtin, F., Mullins, C. S., & Linnebacher, M. (2020). Mouse models of colorectal cancer: Past, present and future perspectives. World Journal of Gastroenterology, 26(13), 1394. Bakrim, S., Machate, H., Benali, T., Sahib, N., Jaouadi, I., Omari, N. E., Aboulaghras, S., Bangar, S. P., Lorenzo, J. M., & Zengin, G. (2022). Natural sources and pharmacological properties of pinosylvin. Plants, 11(12), 1541. Banik, K., Ranaware, A. M., Harsha, C., Nitesh, T., Girisa, S., Deshpande, V., Fan, L., Nalawade, S. P., Sethi, G., & Kunnumakkara, A. B. (2020). Piceatannol: A natural stilbene for the prevention and treatment of cancer. Pharmacological Research, 153, 104635. Barathi, S., Gitanjali, J., Rathinasamy, G., Sabapathi, N., Aruljothi, K., Lee, J., & Kandasamy, S. (2023). Recent trends in polycyclic aromatic hydrocarbons pollution distribution and counteracting bio-remediation strategies. Chemosphere, 139396. Bardelčíková, A., Šoltys, J., & Mojžiš, J. (2023). Oxidative stress, inflammation and colorectal cancer: An overview. Antioxidants, 12(4), 901. Bayrer, J. R., Wang, H., Nattiv, R., Suzawa, M., Escusa, H. S., Fletterick, R. J., Klein, O. D., Moore, D. D., & Ingraham, H. A. (2018). LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival. Nature communications, 9(1), 4055. Berry, D., Schwab, C., Milinovich, G., Reichert, J., Ben Mahfoudh, K., Decker, T., Engel, M., Hai, B., Hainzl, E., & Heider, S. (2012). Phylotype-level 16S rRNA analysis reveals new bacterial indicators of health state in acute murine colitis. The ISME journal, 6(11), 2091-2106. Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 74(3), 229-263. Buhrmann, C., Shayan, P., Kraehe, P., Popper, B., Goel, A., & Shakibaei, M. (2015). Resveratrol induces chemosensitization to 5-fluorouracil through up-regulation of intercellular junctions, Epithelial-to-mesenchymal transition and apoptosis in colorectal cancer. Biochemical Pharmacology, 98(1), 51-68. Buhrmann, C., Yazdi, M., Popper, B., Kunnumakkara, A. B., Aggarwal, B. B., & Shakibaei, M. (2019). Induction of the epithelial-to-mesenchymal transition of human colorectal cancer by human TNF-β (lymphotoxin) and its reversal by resveratrol. Nutrients, 11(3), 704. Bukowska, B., Mokra, K., & Michałowicz, J. (2022). Benzo [a] pyrene—Environmental occurrence, human exposure, and mechanisms of toxicity. International journal of molecular sciences, 23(11), 6348. Candi, E., Schmidt, R., & Melino, G. (2005). The cornified envelope: a model of cell death in the skin. Nature reviews Molecular cell biology, 6(4), 328-340. Caprara, G. (2021). Mediterranean-type dietary pattern and physical activity: The winning combination to counteract the rising burden of non-communicable diseases (NCDS). Nutrients, 13(2), 429. Carr, P. R., Weigl, K., Jansen, L., Walter, V., Erben, V., Chang-Claude, J., Brenner, H., & Hoffmeister, M. (2018). Healthy lifestyle factors associated with lower risk of colorectal cancer irrespective of genetic risk. Gastroenterology, 155(6), 1805-1815. e1805. Casteleyn, C., Rekecki, A., Van der Aa, A., Simoens, P., & Van Den Broeck, W. (2010). Surface area assessment of the murine intestinal tract as a prerequisite for oral dose translation from mouse to man. Laboratory Animals, 44(3), 176-183. Cavalieri, E., Stack, D., Devanesan, P., Todorovic, R., Dwivedy, I., Higginbotham, S., Johansson, S., Patil, K., Gross, M., & Gooden, J. (1997). Molecular origin of cancer: catechol estrogen-3, 4-quinones as endogenous tumor initiators. Proceedings of the National Academy of Sciences, 94(20), 10937-10942. Chang, C. H., Lien, Y. T., Lin, W. S., Nagabhushanam, K., Ho, C. T., & Pan, M. H. (2023). Protective Effects of Piceatannol on DNA Damage in Benzo [a] pyrene-Induced Human Colon Epithelial Cells. Journal of Agricultural and Food Chemistry, 71(19), 7370-7381. Chassaing, B., Aitken, J. D., Malleshappa, M., & Vijay‐Kumar, M. (2014). Dextran sulfate sodium (DSS)‐induced colitis in mice. Current Protocols in Immunology, 104(1), 15.25. 11-15.25. 14. Cheng, Y., Ling, Z., & Li, L. (2020). The intestinal microbiota and colorectal cancer. Frontiers in Immunology, 11, 615056. Chiou, Y. S., Tsai, M. L., Nagabhushanam, K., Wang, Y. J., Wu, C. H., Ho, C. T., & Pan, M. H. (2011). Pterostilbene is more potent than resveratrol in preventing azoxymethane (AOM)-induced colon tumorigenesis via activation of the NF-E2-related factor 2 (Nrf2)-mediated antioxidant signaling pathway. Journal of Agricultural and Food Chemistry, 59(6), 2725-2733. Cháirez-Ramírez, M. H., de la Cruz-López, K. G., & García-Carrancá, A. (2021). Polyphenols as antitumor agents targeting key players in cancer-driving signaling pathways. Frontiers in Pharmacology, 12, 710304. Choi, K. J., Yoon, M. Y., Kim, J. E., & Yoon, S. S. (2023). Gut commensal Kineothrix alysoides mitigates liver dysfunction by restoring lipid metabolism and gut microbial balance. Scientific Reports, 13(1), 14668. Choi, S. I., Kim, N., Nam, R. H., Jang, J. Y., Kim, E. H., Ha, S., Kang, K., Lee, W., Choi, H., & Kim, Y.-R. (2023). The protective effect of Roseburia faecis against repeated water avoidance stress-induced irritable bowel syndrome in a wister rat model. Journal of Cancer Prevention, 28(3), 93. Choo, Q. Y., Yeo, S. C. M., Ho, P. C., Tanaka, Y., & Lin, H. S. (2014). Pterostilbene surpassed resveratrol for anti-inflammatory application: potency consideration and pharmacokinetics perspective. Journal of Functional Foods, 11, 352-362. Chou, Y. C., Lin, Y. H., Lin, P. H., Tung, Y. C., Ho, C. T., & Pan, M. H. (2021). Dietary 5-demethylnobiletin modulates xenobiotic-metabolizing enzymes and ameliorates colon carcinogenesis in benzo [a] pyrene-induced mice. Food and Chemical Toxicology, 155, 112380. Chu, J., Feng, S., Guo, C., Xue, B., He, K., & Li, L. (2023). Immunological mechanisms of inflammatory diseases caused by gut microbiota dysbiosis: A review. Biomedicine and Pharmacotherapy, 164, 114985. Chung, Y., Ryu, Y., An, B. C., Yoon, Y.-S., Choi, O., Kim, T. Y., Yoon, J., Ahn, J. Y., Park, H. J., & Kwon, S.-K. (2021). A synthetic probiotic engineered for colorectal cancer therapy modulates gut microbiota. Microbiome, 9(1), 122. Ciolino, H. P., & Yeh, G. C. (1999). Inhibition of aryl hydrocarbon-induced cytochrome P-450 1A1 enzyme activity and CYP1A1 expression by resveratrol. Molecular Pharmacology, 56(4), 760-767. Cooper H. S., M. S. N., Shah R. S., Sedergran D. J. (1993). Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Laboratory Investigation, 69(2), 238-249. Cuevas-Ramos, G., Petit, C. R., Marcq, I., Boury, M., Oswald, E., & Nougayrède, J.-P. (2010). Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proceedings of the National Academy of Sciences, 107(25), 11537-11542. Das, D. N., & Ravi, N. (2022). Influences of polycyclic aromatic hydrocarbon on the epigenome toxicity and its applicability in human health risk assessment. Environmental Research, 213, 113677. Dave, A., Park, E.-J., & Pezzuto, J. M. (2023). Multi-Organ Nutrigenomic Effects of Dietary Grapes in a Mouse Model. Antioxidants, 12(10), 1821. DeGroff, A., Sharma, K., Satsangi, A., Kenney, K., Joseph, D., Ross, K., Leadbetter, S., Helsel, W., Kammerer, W., & Firth, R. (2018). Increasing colorectal cancer screening in health care systems using evidence-based interventions. Preventing Chronic Disease, 15, E100. Dhanapal, J., & Balaraman Ravindrran, M. (2018). Chitosan/poly (lactic acid)-coated piceatannol nanoparticles exert an in vitro apoptosis activity on liver, lung and breast cancer cell lines. Artificial Cells Nanomedicine and Biotechnology, 46(sup1), 274-282. Ding, Q., Lu, P., Xia, Y., Ding, S., Fan, Y., Li, X., Han, P., Liu, J., Tian, D., & Liu, M. (2016). CXCL9: evidence and contradictions for its role in tumor progression. Cancer medicine, 5(11), 3246-3259. Domingo, J. L., & Nadal, M. (2015). Human dietary exposure to polycyclic aromatic hydrocarbons: A review of the scientific literature. Food and Chemical Toxicology, 86, 144-153. Dos Santos, F. A., Xavier, J. A., da Silva, F. C., Merlin, J., Goulart, M. O., & Rupasinghe, H. (2022). Antidiabetic, antiglycation, and antioxidant activities of ethanolic seed extract of Passiflora edulis and piceatannol in vitro. Molecules, 27(13), 4064. Drwal, E., Rak, A., & Gregoraszczuk, E. L. (2019). Polycyclic aromatic hydrocarbons (PAHs)—Action on placental function and health risks in future life of newborns. Toxicology, 411, 133-142. Du, M., Zhang, Z., & Gao, T. (2017). Piceatannol induced apoptosis through up-regulation of microRNA-181a in melanoma cells. Biological Research, 50(1), 36-36. Eichele, D. D., & Kharbanda, K. K. (2017). Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis. World Journal of Gastroenterology, 23(33), 6016. El-Readi, M. Z., Eid, S., Abdelghany, A. A., Al-Amoudi, H. S., Efferth, T., & Wink, M. (2019). Resveratrol mediated cancer cell apoptosis, and modulation of multidrug resistance proteins and metabolic enzymes. Phytomedicine, 55, 269-281. El Omari, N., El Fessikh, M., Aboulaghras, S., Bakrim, S., Khalid, A., Abdalla, A. N., Goh, K. W., & Bouyahya, A. (2025). The role of inflammation in colorectal cancer and the preventive potential of natural compounds. Journal of Functional Foods, 129, 106857. Erdogan, A., & Lee, Y. Y. (2020). Colon and pelvic floor anatomy and physiology. In Clinical and Basic Neurogastroenterology and Motility (pp. 113-126): Elsevier. Ewels, P., Magnusson, M., Lundin, S., & Käller, M. (2016). MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics, 32(19), 3047-3048. Farombi, E. O., Ajayi, B. O., & Adedara, I. A. (2020). 6-Gingerol delays tumorigenesis in benzo [a] pyrene and dextran sulphate sodium-induced colorectal cancer in mice. Food and Chemical Toxicology, 142, 111483. Farrand, L., Byun, S., Kim, J. Y., Im Aram, A., Lee, J., Lim, S., Lee, K. W., Suh, J. Y., Lee, H. J., & Tsang, B. K. (2013). Piceatannol enhances cisplatin sensitivity in ovarian cancer via modulation of p53, X-linked inhibitor of apoptosis protein (XIAP), and mitochondrial fission. Journal of Biological Chemistry, 288(33), 23740-23750. Fearon, E. R., & Vogelstein, B. (1990). A genetic model for colorectal tumorigenesis. Cell, 61(5), 759-767. Feng, Y., Ji, D., Huang, Y., Ji, B., Zhang, Y., Li, J., Peng, W., Zhang, C., Zhang, D., & Sun, Y. (2020). TGM3 functions as a tumor suppressor by repressing epithelial‑to‑mesenchymal transition and the PI3K/AKT signaling pathway in colorectal cancer. Oncology Reports, 43(3), 864-876. Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Piñeros M, Z. A., Soerjomataram I, & F, B. (2024). Global Cancer Observatory: Cancer Today (version 1.1). Retrieved from https://gco.iarc.who.int/today, (accessed 19 Oct 2025). Fidler, M. M., Soerjomataram, I., & Bray, F. (2016). A global view on cancer incidence and national levels of the human development index. International Journal of Cancer, 139(11), 2436-2446. Fu, C., Li, Y., Xi, H., Niu, Z., Chen, N., Wang, R., Yan, Y., Gan, X., Wang, M., & Zhang, W. (2022). Benzo (a) pyrene and cardiovascular diseases: An overview of pre-clinical studies focused on the underlying molecular mechanism. Frontiers in nutrition, 9, 978475. García‐Villalba, R., Giménez‐Bastida, J. A., García‐Conesa, M. T., Tomás‐Barberán, F. A., Carlos Espin, J., & Larrosa, M. (2012). Alternative method for gas chromatography‐mass spectrometry analysis of short‐chain fatty acids in faecal samples. Journal of separation science, 35(15), 1906-1913. Geahlen, R. L., & McLaughlin, J. L. (1989). Piceatannol (3, 4, 3′, 5′-tetrahydroxy-trans-stilbene) is a naturally occurring protein-tyrosine kinase inhibitor. Biochemical and Biophysical Research Communications, 165(1), 241-245. Gelmez, E., Jeron, A., & Bruder, D. (2022). Negative elongation factor: a key factor in the maintenance of intestinal epithelial barrier integrity. Cellular & Molecular Immunology, 19(4), 453-455. Gene Ontology, C. (2008). The gene ontology project in 2008. Nucleic Acids Research, 36(Database issue), D440-444. George, B. P., Chandran, R., & Abrahamse, H. (2021). Role of phytochemicals in cancer chemoprevention: Insights. Antioxidants, 10(9), 1455. Griffin, M., Casadio, R., & Bergamini, C. M. (2002). Transglutaminases: nature’s biological glues. Biochemical Journal, 368(2), 377-396. Guo, B., Feng, D., Xu, Z., Qi, P., & Yan, X. (2021). Acute benzo [a] pyrene exposure induced oxidative stress, neurotoxicity and epigenetic change in blood clam Tegillarca granosa. Scientific Reports, 11(1), 18744. Haas, K. N., & Blanchard, J. L. (2017). Kineothrix alysoides, gen. nov., sp. nov., a saccharolytic butyrate-producer within the family Lachnospiraceae. International journal of systematic and evolutionary microbiology, 67(2), 402-410. Haboubi, N., & Salmo, E. (2018). Pathology and Staging of Colorectal Adenoma and Adenocarcinoma. In Keighley & Williams' Surgery of the Anus, Rectum and Colon, Fourth Edition (pp. 511-531): CRC Press. Hakura, A., Seki, Y., Sonoda, J., Hosokawa, S., Aoki, T., Suganuma, A., Kerns, W. D., & Tsukidate, K. (2011). Rapid induction of colonic adenocarcinoma in mice exposed to benzo [a] pyrene and dextran sulfate sodium. Food and Chemical Toxicology, 49(11), 2997-3001. Harris, D. L., Washington, M. K., Hood, D. B., Roberts, L. J., & Ramesh, A. (2009). Dietary Fat–Influenced Development of Colon Neoplasia in Apc Min Mice Exposed to Benzo (a) pyrene. Toxicologic Pathology, 37(7), 938-946. Harris, I. S., & DeNicola, G. M. (2020). The complex interplay between antioxidants and ROS in cancer. Trends in Cell Biology, 30(6), 440-451. Harris, K. L., Harris, K. J., Banks, L. D., Adunyah, S. E., & Ramesh, A. (2024). Acceleration of benzo (a) pyrene-induced colon carcinogenesis by Western diet in a rat model of colon cancer. Current Research in Toxicology, 6, 100162. Hill, S., Reichermeier, K., Scott, D. C., Samentar, L., Coulombe-Huntington, J., Izzi, L., Tang, X., Ibarra, R., Bertomeu, T., & Moradian, A. (2019). Robust cullin-RING ligase function is established by a multiplicity of poly-ubiquitylation pathways. eLife, 8, e51163. Hillman, E. T., Kozik, A. J., Hooker, C. A., Burnett, J. L., Heo, Y., Kiesel, V. A., Nevins, C. J., Oshiro, J. M., Robins, M. M., & Thakkar, R. D. (2020). Comparative genomics of the genus Roseburia reveals divergent biosynthetic pathways that may influence colonic competition among species. Microbial genomics, 6(7), e000399. Hossain, M. S., Karuniawati, H., Jairoun, A. A., Urbi, Z., Ooi, D. J., John, A., Lim, Y. C., Kibria, K. K., Mohiuddin, A., & Ming, L. C. (2022). Colorectal cancer: a review of carcinogenesis, global epidemiology, current challenges, risk factors, preventive and treatment strategies. Cancers, 14(7), 1732. Housseau, F., Wu, S., Wick, E. C., Fan, H., Wu, X., Llosa, N. J., Smith, K. N., Tam, A., Ganguly, S., & Wanyiri, J. W. (2016). Redundant innate and adaptive sources of IL17 production drive colon tumorigenesis. Cancer Research, 76(8), 2115-2124. Hsieh, T. C., Lin, C. Y., Lin, H. Y., & Wu, J. M. (2012). AKT/mTOR as novel targets of polyphenol piceatannol possibly contributing to inhibition of proliferation of cultured prostate cancer cells. International Scholarly Research Notices, 2012(1), 272697. Hu, W. H., Dai, D. K., Zheng, B. Z. Y., Duan, R., Dong, T. T. X., Qin, Q. W., & Tsim, K. W. K. (2020). Piceatannol, a natural analog of resveratrol, exerts anti-angiogenic efficiencies by blockage of vascular endothelial growth factor binding to its receptor. Molecules 25(17), 3769. Huang, G., & Elferink, C. J. (2012). A novel nonconsensus xenobiotic response element capable of mediating aryl hydrocarbon receptor-dependent gene expression. Molecular Pharmacology, 81(3), 338-347. Huderson, A. C., Rekha Devi, P. V., Niaz, M. S., Adunyah, S. E., & Ramesh, A. (2019). Alteration of benzo(a)pyrene biotransformation by resveratrol in ApcMin/+ mouse model of colon carcinogenesis. Investigational New Drugs, 37(2), 238-251. Hugenholtz, F., & de Vos, W. M. (2018). Mouse models for human intestinal microbiota research: a critical evaluation. Cellular and Molecular Life Sciences, 75(1), 149-160. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. (2012). Benzene (Available from: https://www.ncbi.nlm.nih.gov/books/NBK304415/ ed. Vol. 100F). Lyon, France: International Agency for Research on Cancer. Jang, S., Han, H., Oh, Y., & Kim, Y. (2024). Sex differences in inflammation correlated with estrogen and estrogen receptor-β levels in azoxymethane/dextran sodium sulfate-induced colitis-associated colorectal cancer mice. Heliyon, 10(6). Jauregui-Amezaga, A., Geerits, A., Das, Y., Lemmens, B., Sagaert, X., Bessissow, T., Lobatón, T., Ferrante, M., Van Assche, G., & Bisschops, R. (2017). A simplified Geboes score for ulcerative colitis. Journal of Crohn's and Colitis, 11(3), 305-313. Jean Eric Ghia, P. B., Harry Kumar–Ondiveeran, Elena F.Verdu, Stephen M. Collins. (2006). The Vagus Nerve: A Tonic Inhibitory Influence Associated With Inflammatory Bowel Disease in a Murine Model. Gastroenterology, 131(4), 1122-1130. Jeong, S. O., Son, Y., Lee, J. H., Cheong, Y. K., Park, S. H., Chung, H. T., & Pae, H. O. (2015). Resveratrol analog piceatannol restores the palmitic acid-induced impairment of insulin signaling and production of endothelial nitric oxide via activation of anti-inflammatory and antioxidative heme oxygenase-1 in human endothelial cells. Molecular Medicine Reports, 12(1), 937-944. Kanehisa, M., Furumichi, M., Sato, Y., Ishiguro-Watanabe, M., & Tanabe, M. (2021). KEGG: integrating viruses and cellular organisms. Nucleic Acids Research, 49(D1), D545-D551. Katsaounou, K., Nicolaou, E., Vogazianos, P., Brown, C., Stavrou, M., Teloni, S., Hatzis, P., Agapiou, A., Fragkou, E., & Tsiaoussis, G. (2022). Colon cancer: From epidemiology to prevention. Metabolites, 12(6), 499. Keller, D., Windsor, A., Cohen, R., & Chand, M. (2019). Colorectal cancer in inflammatory bowel disease: review of the evidence. Techniques in Coloproctology, 23, 3-13. Kelloff, G. J., Hawk, E. T., Karp, J. E., Crowell, J. A., Boone, C. W., Steele, V. E., Lubet, R. A., & Sigman, C. C. (1997). Progress in clinical chemoprevention. Seminars in Oncology, 24(2), 241-252. Kendall, D. G. (1960). Birth-and-death processes, and the theory of carcinogenesis. Biometrika, 47(1/2), 13-21. Keum, N., & Giovannucci, E. (2019). Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nature Reviews: Gastroenterology & Hepatology, 16(12), 713-732. Kido, L. A., Hahm, E. R., Kim, S. H., Baseggio, A. M., Cagnon, V. H. A., Singh, S. V., & Maróstica, M. R. (2020). Prevention of prostate cancer in transgenic adenocarcinoma of the mouse prostate mice by yellow passion fruit extract and antiproliferative effects of its bioactive compound piceatannol. Journal of Cancer Prevention, 25(2), 87-99. Kimura, Y. (2022). Long-Term Oral Administration of Piceatannol (3,5,3′,4′-Tetrahydroxystilbene) Attenuates Colon Tumor Growth Induced by Azoxymethane Plus Dextran Sulfate Sodium in C57BL/6J Mice. Nutrition and Cancer, 74(6), 2184-2195. Ko, H. S., Lee, H. J., Kim, S. H., & Lee, E. O. (2012). Piceatannol suppresses breast cancer cell invasion through the inhibition of MMP-9: involvement of PI3K/AKT and NF-κB pathways. Journal of Agricultural and Food Chemistry, 60(16), 4083-4089. Koh, Y. C., Ho, C. T., & Pan, M. H. (2020). Recent advances in cancer chemoprevention with phytochemicals. Journal of Food and Drug Analysis, 28(1), 14-37. Koh, Y. C., Lin, S. J., Hsu, K. Y., Nagabhushanam, K., Ho, C. T., & Pan, M. H. (2023). Pterostilbene Enhances Thermogenesis and Mitochondrial Biogenesis by Activating the SIRT1/PGC‐1α/SIRT3 Pathway to Prevent Western Diet‐Induced Obesity. Molecular Nutrition & Food Research, 67(18), 2300370. Koyama, N., Hakura, A., Toritsuka, N., Sonoda, J., Seki, Y., Tohyama, O., Asakura, S., Nakano-Ito, K., & Hosokawa, S. (2015). Wif1 and Ifitm3 gene expression preferentially altered in the colon mucosa of benzo [a] pyrene pre-treated mice following exposure to dextran sulfate sodium. Chemico-Biological Interactions, 240, 164-170. Kuppusamy, S., Thavamani, P., Megharaj, M., & Naidu, R. (2016). Biodegradation of polycyclic aromatic hydrocarbons (PAHs) by novel bacterial consortia tolerant to diverse physical settings–assessments in liquid-and slurry-phase systems. International Biodeterioration & Biodegradation, 108, 149-157. Lawal, A. T. (2017). Polycyclic aromatic hydrocarbons. A review. Cogent Environmental Science, 3(1), 1339841. Lee, Y. J., Kim, W. R., Park, E. G., Lee, D. H., Kim, J.-m., Shin, H. J., Jeong, H.-s., Roh, H.-Y., & Kim, H.-S. (2024). Exploring the Key Signaling Pathways and ncRNAs in Colorectal Cancer. International journal of molecular sciences, 25(8), 4548. Leiphrakpam, P. D., & Are, C. (2024). PI3K/Akt/mTOR Signaling Pathway as a Target for Colorectal Cancer Treatment. International journal of molecular sciences, 25(6), 3178. Li, J., Zhang, Z., Wang, L., & Zhang, Y. (2019). The oncogenic role of Wnt10a in colorectal cancer through activation of canonical Wnt/β‑catenin signaling. Oncology Letters, 17(4), 3657-3664. Li, L., Wang, M., Chen, J., Xu, Z., Wang, S., Xia, X., Liu, D., Wang, S., Xie, C., & Wu, J. (2021). Preventive effects of bacillus licheniformis on heat stroke in rats by sustaining intestinal barrier function and modulating gut microbiota. Frontiers in Microbiology, 12, 630841. Liao, M. J., Dong, H., & Chen, G. (2025). Mechanisms and advantages of natural derived small molecule compounds in the prevention and treatment of colorectal cancer: a review. Frontiers in Pharmacology, 16, 1658493. Lin, W. S., Chueh, T. L., Nagabhushanam, K., Ho, C. T., & Pan, M. H. (2023). Piceatannol and 3′-hydroxypterostilbene alleviate inflammatory bowel disease by maintaining intestinal epithelial integrity and regulating gut microbiota in mice. Journal of Agricultural and Food Chemistry, 71(4), 1994-2005. Liu, Q., Yang, C., Wang, S., Shi, D., Wei, C., Song, J., Lin, X., Dou, R., Bai, J., & Xiang, Z. (2020). Wnt5a-induced M2 polarization of tumor-associated macrophages via IL-10 promotes colorectal cancer progression. Cell Communication and Signaling, 18(1), 51. Liu, Y., Yin, T., Feng, Y., Cona, M. M., Huang, G., Liu, J., Song, S., Jiang, Y., Xia, Q., & Swinnen, J. V. (2015). Mammalian models of chemically induced primary malignancies exploitable for imaging-based preclinical theragnostic research. Quantitative imaging in medicine and surgery, 5(5), 708. Liu, Y. Z., Wu, K., Huang, J., Liu, Y., Wang, X., Meng, Z. J., Yuan, S. X., Wang, D. X., Luo, J. Y., & Zuo, G. W. (2014). The PTEN/PI3K/Akt and Wnt/β-catenin signaling pathways are involved in the inhibitory effect of resveratrol on human colon cancer cell proliferation. International Journal of Oncology, 45(1), 104-112. Lucas, J., Hsieh, T. C., Halicka, H. D., Darzynkiewicz, Z., & Wu, J. M. (2018). Upregulation of PD‑L1 expression by resveratrol and piceatannol in breast and colorectal cancer cells occurs via HDAC3/p300‑mediated NF‑κB signaling. International Journal of Oncology, 53(4), 1469-1480. Luch, A. (2005). Nature and nurture–lessons from chemical carcinogenesis. Nature Reviews Cancer, 5(2), 113-125. Ma, L., Zhang, M., Zhao, R., Wang, D., Ma, Y., & Ai, L. (2021). Plant natural products: Promising resources for cancer chemoprevention. Molecules, 26(4), 933. Malki, A., ElRuz, R. A., Gupta, I., Allouch, A., Vranic, S., & Al Moustafa, A. E. (2020). Molecular mechanisms of colon cancer progression and metastasis: recent insights and advancements. International journal of molecular sciences, 22(1), 130. Marioni, J. C., Mason, C. E., Mane, S. M., Stephens, M., & Gilad, Y. (2008). RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome research, 18(9), 1509-1517. Marshall, J. S., Warrington, R., Watson, W., & Kim, H. L. (2018). An introduction to immunology and immunopathology. Allergy, Asthma & Clinical Immunology, 14, 1-10. Meng, T., Wen, Z., Cheng, X., Li, C., Zhang, P., Xiao, D., & Xu, Y. (2025). Unlocking Gut Health: The Potent Role of Stilbenoids in Intestinal Homeostasis. Animals, 15(3), 417. Moolgavkar, S., & Luebeck, G. (2020). Multistage carcinogenesis: a unified framework for cancer data analysis. Statistical Modeling for Biological Systems: In Memory of Andrei Yakovlev, 117-136. Murray, I. A., Patterson, A. D., & Perdew, G. H. (2014). Aryl hydrocarbon receptor ligands in cancer: friend and foe. Nature Reviews Cancer, 14(12), 801-814. Murthy S. N., C. H. S., Shim H., Shah R. S., Ibrahim S. A., Sedergran D. J. (1993). Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin. Digestive diseases and sciences, 38(9), 1722-1734. Naber, A., & De Jong, D. (2003). Assessment of disease activity in inflammatory bowel disease; relevance for clinical trials. Netherlands Journal of Medicine, 61(4), 105-110. Nakagama, H., Nakanishi, M., & Ochiai, M. (2005). Modeling human colon cancer in rodents using a food‐borne carcinogen, PhIP. Cancer Science, 96(10), 627-636. Nakayama, M., & Oshima, M. (2019). Mutant p53 in colon cancer. Journal of Molecular Cell Biology, 11(4), 267-276. Neto, Í., Rocha, J., Gaspar, M. M., & Reis, C. P. (2023). Experimental murine models for colorectal cancer research. Cancers, 15(9), 2570. Nguyen, H. T., & Duong, H. Q. (2018). The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy. Oncology Letters, 16(1), 9-18. Nguyen, T. L. A., Vieira-Silva, S., Liston, A., & Raes, J. (2015). How informative is the mouse for human gut microbiota research? Disease Models & Mechanisms, 8(1), 1-16. Niles, R. M., Cook, C. P., Meadows, G. G., Fu, Y. M., McLaughlin, J. L., & Rankin, G. O. (2006). Resveratrol is rapidly metabolized in athymic (nu/nu) mice and does not inhibit human melanoma xenograft tumor growth. The Journal of Nutrition, 136(10), 2542-2546. Nutakul, W., Sobers, H. S., Qiu, P., Dong, P., Decker, E. A., McClements, D. J., & Xiao, H. (2011). Inhibitory effects of resveratrol and pterostilbene on human colon cancer cells: a side-by-side comparison. Journal of Agricultural and Food Chemistry, 59(20), 10964-10970. Oliveira, R. C., Abrantes, A. M., Tralhão, J. G., & Botelho, M. F. (2020). The role of mouse models in colorectal cancer research—The need and the importance of the orthotopic models. Animal Models and Experimental Medicine, 3(1), 1-8. Park, E. J., Chung, H. J., Park, H. J., Kim, G. D., Ahn, Y. H., & Lee, S. K. (2013). Suppression of Src/ERK and GSK-3/β-catenin signaling by pinosylvin inhibits the growth of human colorectal cancer cells. Food and Chemical Toxicology, 55, 424-433. Park, J., Pyee, J., & Park, H. (2014). Pinosylvin at a high concentration induces AMPK-mediated autophagy for preventing necrosis in bovine aortic endothelial cells. Canadian Journal of Physiology and Pharmacology, 92(12), 993-999. Patel, A. B., Shaikh, S., Jain, K. R., Desai, C., & Madamwar, D. (2020). Polycyclic aromatic hydrocarbons: sources, toxicity, and remediation approaches. Frontiers in Microbiology, 11, 562813. Patra, K. C., & Hay, N. (2014). The pentose phosphate pathway and cancer. Trends in Biochemical Sciences, 39(8), 347-354. Peng, C., Ouyang, Y., Lu, N., & Li, N. (2020). The NF-κB signaling pathway, the microbiota, and gastrointestinal tumorigenesis: recent advances. Frontiers in Immunology, 11, 1387. Piberger, A. L., Krüger, C. T., Strauch, B. M., Schneider, B., & Hartwig, A. (2018). BPDE-induced genotoxicity: relationship between DNA adducts, mutagenicity in the in vitro PIG-A assay, and the transcriptional response to DNA damage in TK6 cells. Archives of Toxicology, 92(1), 541-551. Piotrowska, H., Kucinska, M., & Murias, M. (2012). Biological activity of piceatannol: leaving the shadow of resveratrol. Mutation Research/Reviews in Mutation Research, 750(1), 60-82. Potter, G. A., Patterson, L. H., Wanogho, E., Perry, P. J., Butler, P. C., Ijaz, T., Ruparelia, K. C., Lamb, J. H., Farmer, P. B., Stanley, L. A., & Burke, M. D. (2002). The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1. British Journal of Cancer, 86(5), 774-778. Qi, G. X., Zhao, R. X., Gao, C., Ma, Z. Y., Wang, S., & Xu, J. (2025). Recent advances and challenges in colorectal cancer: From molecular research to treatment. World Journal of Gastroenterology, 31(21), 106964. Qi, Y., Zhang, L., Liu, Y., Li, Y., Liu, Y., & Zhang, Z. (2024). Targeted modulation of myeloid-derived suppressor cells in the tumor microenvironment: implications for cancer therapy. Biomedicine and Pharmacotherapy, 180, 117590. Richmond, A., & Su, Y. (2008). Mouse xenograft models vs GEM models for human cancer therapeutics. Disease Models & Mechanisms, 1(2-3), 78-82. Rigi, P., Kamani, H., Ansari, H., Mohammadi, L., & Dargahi, A. (2025). Health risk assessment of polycyclic aromatic hydrocarbon compounds (PAHs) in grilled meats in Zahedan city of Iran. Scientific Reports, 15(1), 24267. Roberts, S. M., James, R. C., & Williams, P. L. (2022). Principles of toxicology: environmental and industrial applications: John Wiley & Sons. Rossi, M., Caruso, F., Opazo, C., & Salciccioli, J. (2008). Crystal and molecular structure of piceatannol; scavenging features of resveratrol and piceatannol on hydroxyl and peroxyl radicals and docking with transthyretin. Journal of Agricultural and Food Chemistry, 56(22), 10557-10566. Salazar, J. H. (2014). Overview of urea and creatinine. Laboratory Medicine, 45(1), e19-e20. Sawicki, T., Ruszkowska, M., Danielewicz, A., Niedźwiedzka, E., Arłukowicz, T., & Przybyłowicz, K. E. (2021). A review of colorectal cancer in terms of epidemiology, risk factors, development, symptoms and diagnosis. Cancers, 13(9), 2025. Schmitt, M., & Greten, F. R. (2021). The inflammatory pathogenesis of colorectal cancer. Nature Reviews Immunology, 21(10), 653-667. Setoguchi, Y., Oritani, Y., Ito, R., Inagaki, H., Maruki-Uchida, H., Ichiyanagi, T., & Ito, T. (2014). Absorption and Metabolism of Piceatannol in Rats. Journal of Agricultural and Food Chemistry, 62(12), 2541-2548. Seyed, M. A., Jantan, I., Bukhari, S. N. A., & Vijayaraghavan, K. (2016). A comprehensive review on the chemotherapeutic potential of piceatannol for cancer treatment, with mechanistic insights. Journal of Agricultural and Food Chemistry, 64(4), 725-737. Siddiqui, I. A., Sanna, V., Ahmad, N., Sechi, M., & Mukhtar, H. (2015). Resveratrol nanoformulation for cancer prevention and therapy. Annals of the New York Academy of Sciences, 1348(1), 20-31. Siddiqui, R., Boghossian, A., Alharbi, A. M., Alfahemi, H., & Khan, N. A. (2022). The pivotal role of the gut microbiome in colorectal cancer. Biology, 11(11), 1642. Singh, S. P., Chand, H. S., Banerjee, S., Agarwal, H., Raizada, V., Roy, S., & Sopori, M. (2020). Acetylcholinesterase inhibitor pyridostigmine bromide attenuates gut pathology and bacterial dysbiosis in a murine model of ulcerative colitis. Digestive diseases and sciences, 65(1), 141-149. Sporn, M. B., Dunlop, N., Newton, D., & Smith, J. (1976). Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Paper presented at the Federation Proceedings. Steward, W., & Brown, K. (2013). Cancer chemoprevention: a rapidly evolving field. British Journal of Cancer, 109(1), 1-7. Straif, K., Baan, R., Grosse, Y., Secretan, B., El Ghissassi, F., & Cogliano, V. (2005). Carcinogenicity of polycyclic aromatic hydrocarbons. The lancet oncology, 6(12), 931-932. Sueishi, Y., Nii, R., & Kakizaki, N. (2017). Resveratrol analogues like piceatannol are potent antioxidants as quantitatively demonstrated through the high scavenging ability against reactive oxygen species and methyl radical. Bioorganic and Medicinal Chemistry Letters, 27(23), 5203-5206. Surien, O., Masre, S. F., Basri, D. F., & Ghazali, A. R. (2022). Chemopreventive effects of oral pterostilbene in multistage carcinogenesis of skin squamous cell carcinoma mouse model induced by DMBA/TPA. Biomedicines, 10(11), 2743. Temiz, T. K., Altun, A., Turgut, N., & Balcı, E. (2014). Investigation of the effects of drugs effective on PI3K-AKT signaling pathway in colorectal cancer alone and in combination. Cumhuriyet Medical Journal, 36(2), 167-177. Thélin, C., & Sikka, S. (2015). Epidemiology of colorectal Cancer—incidence, lifetime risk factors statistics and temporal trends. Screening for colorectal Cancer with colonoscopy. London: IntechOpen Limited, 61-77. Uribe, M. L., Marrocco, I., & Yarden, Y. (2021). EGFR in cancer: Signaling mechanisms, drugs, and acquired resistance. Cancers, 13(11), 2748. Valenta, T., Hausmann, G., & Basler, K. (2012). The many faces and functions of β‐catenin. The EMBO journal, 31(12), 2714-2736. Vogelstein, B., Fearon, E. R., Hamilton, S. R., Kern, S. E., Preisinger, A. C., Leppert, M., Smits, A. M., & Bos, J. L. (1988). Genetic alterations during colorectal-tumor development. New England Journal of Medicine, 319(9), 525-532. Wang, B., & Li, J. (2020). Piceatannol suppresses the proliferation and induced apoptosis of osteosarcoma cells through PI3K/AKT/mTOR pathway. Cancer Management and Research, 2631-2640. Wang, B., Rong, X., Palladino, E. N., Wang, J., Fogelman, A. M., Martín, M. G., Alrefai, W. A., Ford, D. A., & Tontonoz, P. (2018). Phospholipid remodeling and cholesterol availability regulate intestinal stemness and tumorigenesis. Cell stem cell, 22(2), 206-220.e204. Wang, Z., Zhao, Q., Nie, Y., Yu, Y., Misra, B. B., Zabalawi, M., Chou, J. W., Key, C.-C. C., Molina, A. J., & Quinn, M. A. (2020). Solute carrier family 37 member 2 (SLC37A2) negatively regulates murine macrophage inflammation by controlling glycolysis. Iscience, 23(5), 101125. Wattenberg, L. W. (1966). Chemoprophylaxis of carcinogenesis: a review. Cancer Research, 26(7_Part_1), 1520-1526. Wawszczyk, J., Jesse, K., Smolik, S., & Kapral, M. (2022). Mechanism of pterostilbene-induced cell death in HT-29 colon cancer cells. Molecules, 27(2), 369. Wong, M. C., Huang, J., Lok, V., Wang, J., Fung, F., Ding, H., & Zheng, Z. J. (2021). Differences in incidence and mortality trends of colorectal cancer worldwide based on sex, age, and anatomic location. Clinical Gastroenterology and Hepatology, 19(5), 955-966. e961. Woting, A., & Blaut, M. (2018). Small intestinal permeability and gut-transit time determined with low and high molecular weight fluorescein isothiocyanate-dextrans in C3H mice. Nutrients, 10(6), 685. Wu, G. D., Chen, J., Hoffmann, C., Bittinger, K., Chen, Y. Y., Keilbaugh, S. A., Bewtra, M., Knights, D., Walters, W. A., & Knight, R. (2011). Linking long-term dietary patterns with gut microbial enterotypes. Science, 334(6052), 105-108. Wu, J. C., Tsai, M. L., Lai, C. S., Lo, C. Y., Ho, C. T., Wang, Y. J., & Pan, M. H. (2018). Polymethoxyflavones prevent benzo [a] pyrene/dextran sodium sulfate‐induced colorectal carcinogenesis through modulating xenobiotic metabolism and ameliorate autophagic defect in ICR mice. International Journal of Cancer, 142(8), 1689-1701. Xu, X., Peng, J., Wang, N., Ocansey, D. K. W., Zhang, X., & Mao, F. (2024). hucMSC-Ex alleviates inflammatory bowel disease in mice by enhancing M2-type macrophage polarization via the METTL3-Slc37a2-YTHDF1 axis. Cell Biology and Toxicology, 40(1), 74. Youn, J., Lee, J. S., Na, H. K., Kundu, J. K., & Surh, Y. J. (2009). Resveratrol and Piceatannol Inhibit iNOS Expression and NF-κ B Activation in Dextran Sulfate Sodium-Induced Mouse Colitis. Nutrition and Cancer, 61(6), 847-854. Yu, X., Xu, M., Gao, Z., Guan, H., & Zhu, Q. (2025). Advances in antitumor effects of pterostilbene and its derivatives. Future Medicinal Chemistry, 17(1), 109-124. Zhang, L., Jin, Y., Huang, M., & Penning, T. M. (2012). The role of human aldo-keto reductases in the metabolic activation and detoxication of polycyclic aromatic hydrocarbons: interconversion of PAH catechols and PAH o-quinones. Frontiers in Pharmacology, 3, 32452. Zhang, M., Sun, K., Wu, Y., Yang, Y., Tso, P., & Wu, Z. (2017). Interactions between intestinal microbiota and host immune response in inflammatory bowel disease. Frontiers in Immunology, 8, 942. Zhao, H., Ming, T., Tang, S., Ren, S., Yang, H., Liu, M., Tao, Q., & Xu, H. (2022). Wnt signaling in colorectal cancer: pathogenic role and therapeutic target. Molecular Cancer, 21(1), 144. Zhou, K., Wu, C., Cheng, W., Zhang, B., Wei, R., Cheng, D., Li, Y., Cao, Y., Zhang, W., & Yao, Z. (2024). Transglutaminase 3 regulates cutaneous squamous carcinoma differentiation and inhibits progression via PI3K-AKT signaling pathway-mediated Keratin 14 degradation. Cell Death & Disease, 15(4), 252. Zhou, M., Li, R., Hua, H., Dai, Y., Yin, Z., Li, L., Zeng, J., Yang, M., Zhao, J., & Tan, R. (2024). The role of tetrahydrocurcumin in disease prevention and treatment. Food & Function, 15(13), 6798-6824. Zhu, M., Dang, Y., Yang, Z., Liu, Y., Zhang, L., Xu, Y., Zhou, W., & Ji, G. (2020). Comprehensive RNA sequencing in adenoma-cancer transition identified predictive biomarkers and therapeutic targets of human CRC. Molecular Therapy-Nucleic Acids, 20, 25-33. Zhu, Y., & Li, X. (2023). Advances of Wnt signalling pathway in colorectal cancer. Cells, 12(3), 447. Ziapour, P., Ataee, R., Shadifar, M., Vaillancourt, C., Ahmadi, A., Jafari-Sabet, M., & Ataee, A. (2011). New intracellular and molecular aspects in pathophysiology of colorectal cancer. Gastroenterology and Hepatology from Bed to Bench, 4(2), 43. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/101598 | - |
| dc.description.abstract | 根據世界衛生組織 (World Health Organization, WHO) 2022 年統計資料顯示，大腸直腸癌 (colorectal cancer, CRC) 為全球癌症發生率第三高、死亡率第二高之惡性腫瘤，顯示其對人類健康造成重大威脅。流行病學研究指出，飲食相關致癌物與慢性腸道發炎反應是促進 CRC 發生與進展的重要危險因子。食品加工與高溫烹調過程中所產生之多環芳香烴 (polycyclic aromatic hydrocarbons, PAHs)，可經代謝誘發氧化壓力與促發炎反應，進而活化多條腫瘤相關訊息途徑。其中，苯駢芘(benzo[a]pyrene, B[a]P) 為 PAHs 之代表性致癌物，常與腸道發炎共同促進結腸直腸癌的發生。化學預防 (chemoprevention) 藉由天然或合成化合物抑制發炎反應與致癌過程，已成為癌症預防的重要策略。白皮杉醇 (piceatannol, PIC) 為一種芪類多酚 (stilbenoid)，廣泛存在於葡萄、百香果及白茶中，已被證實具有抗氧化與抗發炎等生物活性。然而，PIC 在發炎相關結腸致癌模型中，不同介入時期之化學預防效果與機制仍缺乏系統性探討。本研究以 B[a]P 與葡聚糖硫酸鈉 (dextran sulfate sodium, DSS) 共同誘導雄性小鼠之發炎相關結腸癌模型，於 18 週內分別在不同致癌階段給予 0.025% PIC，以評估介入時機對腫瘤形成、發炎反應及腸道菌相之影響，並透過 RNA 定序 (RNA-seq) 分析腸道轉錄組變化。結果顯示，持續補充 PIC 可顯著減緩體重流失、降低疾病活動指數 (disease activity index, DAI) 及腫瘤形成，並改善腸道組織形態與上皮屏障功能。PIC 明顯抑制促發炎細胞激素 interleukin-6 (IL-6)、tumor necrosis factor-α (TNF-α) 與 interleukin-1β (IL-1β) 的表現，同時提升抗發炎因子 interleukin-10 (IL-10)，顯示其可有效緩解腸道慢性發炎反應。轉錄組分析顯示，PIC 可下調多條與發炎與腫瘤促進相關之訊息途徑，包括芳香烴受體 (aryl hydrocarbon receptor, AhR)、基質金屬蛋白酶 (matrix metalloproteinases, MMPs)、Wnt 及 PI3K/AKT/mTOR 路徑，並上調與上皮修復與腫瘤抑制相關之轉麩胺酶 3 (transglutaminase 3, TGM3)。蛋白質層級驗證結果進一步證實 PIC 可抑制 PI3K/AKT/mTOR 訊息傳導活化，並促進 TGM3 表現。此外，腸道菌相分析顯示，PIC 可增加具短鏈脂肪酸 (short-chain fatty acids, SCFAs) 產生能力之益生菌，如 Roseburia faecis 與 Kineothrix alysoides，並降低潛在致病菌 Turicibacter sanguinis 與 Romboutsia ilealis 的豐度，進而改善腸道微生態平衡並提升 SCFAs 含量。綜合上述，本研究顯示 PIC 透過抑制發炎反應、調控發炎相關致癌訊息途徑、促進上皮修復及重建腸道菌相平衡，多層次地抑制 B[a]P/DSS 誘導之發炎相關結腸直腸癌發展，突顯其作為天然膳食化學預防劑之應用潛力。 | zh_TW |
| dc.description.abstract | Colorectal cancer (CRC) ranks as the third most frequently diagnosed cancer and the second leading cause of cancer-related mortality worldwide, according to the World Health Organization (WHO, 2022). Accumulating evidence indicates that chronic intestinal inflammation induced by dietary carcinogens is a critical driver of CRC initiation and progression. Polycyclic aromatic hydrocarbons (PAHs), generated during food processing and high-temperature cooking, can induce oxidative stress and pro-inflammatory responses following metabolic activation. Among them, benzo[a]pyrene (B[a]P) is a representative PAH and a well-established carcinogenic marker that synergizes with intestinal inflammation to promote colorectal tumorigenesis. Chemoprevention, which aims to suppress inflammation-associated carcinogenic processes using natural or synthetic compounds, has gained increasing attention. piceatannol (PIC), a naturally occurring stilbenoid polyphenol found in grapes, passion fruit, and white tea, has been reported to exhibit antioxidant and anti-inflammatory activities. However, the chemopreventive efficacy of PIC at different intervention stages and its underlying mechanisms in inflammation-associated CRC remain largely unexplored. In this study, an inflammation-driven CRC model was established using B[a]P combined with dextran sulfate sodium (DSS) in male mice. PIC (0.025%) was administered at different stages over an 18-week period to evaluate the impact of intervention timing on tumor development, inflammatory responses, and gut microbiota composition. Transcriptomic alterations in intestinal tissues were further examined using RNA sequencing (RNA-seq). The results demonstrated that continuous PIC supplementation significantly alleviated body weight loss, reduced disease activity index (DAI) scores, and suppressed tumor formation, accompanied by improvements in intestinal morphology and barrier integrity. Notably, PIC markedly downregulated pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), while upregulating the anti-inflammatory cytokine interleukin-10 (IL-10), indicating effective attenuation of chronic intestinal inflammation. RNA-seq analysis revealed that PIC suppressed multiple inflammation- and tumor-associated signaling pathways, including aryl hydrocarbon receptor (AhR), matrix metalloproteinases (MMPs), Wnt, and PI3K/AKT/mTOR pathways, while enhancing the expression of transglutaminase 3 (TGM3), a gene implicated in epithelial repair and tumor suppression. These findings were further validated at the protein level, confirming that PIC inhibited PI3K/AKT/mTOR activation and promoted TGM3 expression. Moreover, PIC significantly modulated gut microbiota composition by enriching short-chain fatty acids (SCFAs)-producing bacteria, such as Roseburia faecis and Kineothrix alysoides, while reducing potentially pathogenic taxa including Turicibacter sanguinis and Romboutsia ilealis. This microbial reshaping was associated with increased SCFAs production and improved intestinal homeostasis. From the above, these findings demonstrate that PIC exerts multifaceted chemopreventive effects primarily through suppression of inflammation, accompanied by modulation of oncogenic signaling pathways, enhancement of epithelial repair, and restoration of gut microbiota balance. PIC therefore represents a promising dietary chemopreventive agent for inflammation-associated colorectal carcinogenesis. | en |
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| dc.description.provenance | Made available in DSpace on 2026-02-11T16:39:37Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 目次
論文口試委員會審定書 i 誌謝 ii 中文摘要 iv 英文摘要 vi Graphic abstract viii 目次 ix 圖次 xiii 表次 xvii Abbreviation table xviii Chapter 1- Introduction and literature review 1 Section 1- Background of colorectal cancer (CRC) 1 1.1.1 Epidemiological overview of colorectal cancer 1 1.1.2 Overview of the formation of CRC 5 1.1.3 Molecular mechanisms of CRC progression and metastasis 8 Section 2- Contributing factors to CRC 13 1.2.1 Risk factors for CRC 13 1.2.2 Role of gut microbiota in CRC 14 1.2.3 The role of inflammation in CRC development 15 Section 3- Polycyclic aromatic hydrocarbons (PAHs) 18 1.3.1 Induction of PAHs 18 1.3.2 Sources and human exposure of B[a]P 20 1.3.3 Metabolic activation of B[a]P and its carcinogenic mechanism 21 1.3.4 Biological effects of B[a]P and its correlation with CRC 23 Section 4- Multistage colorectal carcinogenesis model 24 1.4.1 Introduction of multistage colorectal carcinogenesis model 24 1.4.2 Common mouse models used in CRC research 25 1.4.3 Comparative physiology and metabolism between mouse and human gastrointestinal tracts 27 1.4.4 Three-phase process of carcinogenesis 31 1.4.5 B[a]P/DSS multistage carcinogenesis model 32 Section 5- Stilbenoids and cancer chemoprevention 33 1.5.1 Introduction to cancer chemoprevention 33 1.5.2 Introduction to Stilbenoids 34 1.5.3 Introduction to PIC 39 1.5.4 Biological benefits of PIC 40 1.5.5 Cancer chemopreventive potential of PIC 41 Chapter 2- Objectives of the study 44 Section 1- The experimental purpose of this study 44 Section 2- Experimental design and framework 47 Chapter 3- Materials and methods 49 Section 1-Material and reagents 49 3.1.1 The source of samples and inducers 49 3.1.2 Instrument 49 3.1.3 Reagents and antibodies 50 3.1.4 Kits 52 Section 2- In vivo B[a]P/DSS induced colon cancer study procedure 52 3.2.1 B[a]P/DSS induced colon cancer experiment methods 52 3.2.2 Experimental animal grouping 53 3.2.3 Disease activity index 53 3.2.4 Animal sacrifice and tissue collection 54 3.2.5 Serum biochemical index and cytokines 55 3.2.6 Intestinal protein extraction 55 3.2.7 Intestinal permeability test 56 3.2.8 Western blotting 57 3.2.9 Hematoxylin-eosin staining 57 3.2.10 Histopathological examination 57 3.2.11 Short chain fatty acids (SCFAs) analysis 59 3.2.12 Gut microbiota analysis 59 3.2.13 Intestinal RNA collection process 60 3.2.14 RNA sequencing and analysis 62 3.2.15 Statistical analysis 63 Chapter 4- Results and discussions 64 4.1 Assessment of body weight changes, organ mass, and serum biochemical parameters in mice with B[a]P/DSS-induced CRC 64 4.2 Effects of PIC intervention at different times on intestinal morphology, tumor burden, and permeability of B[a]P/DSS-induced CRC mice 72 4.3 Histopathological alterations and inflammatory cytokines modulation in B[a]P/DSS-induced colorectal cancer 74 4.4 RNA-Seq analysis of the effects of PIC on intestinal tissue gene expression in B[a]P/DSS-Induced CRC mice 81 4.5 Transcriptomic profiling and differential gene expression in B[a]P/DSS-induced CRC treated with PIC 84 4.6 Functional enrichment and pathway network analyses of PIC-regulated genes 92 4.7 RNA-seq analysis of the effect of PIC on KEGG pathways dotplot and KEGG pathway view of the gene map in B[a]P/DSS -induced CRC 101 4.8 Modulation of the PI3K/AKT/mTOR pathway and Tgm3 expression by PIC in B[a]P/DSS-induced CRC mice 109 4.9 Modulation of gut microbiota and SCFAs by PIC in B[a]P/DSS-induced CRC mice 114 Chapter 5- Conclusion 122 Chapter 6- Future perspectives and research directions 125 References 127 Appendix-Approval of animal use protocol 154 | - |
| dc.language.iso | en | - |
| dc.subject | 白皮杉醇 | - |
| dc.subject | 苯駢芘 | - |
| dc.subject | 結腸直腸癌 | - |
| dc.subject | 癌症化學預防 | - |
| dc.subject | 腸道菌相 | - |
| dc.subject | piceatannol | - |
| dc.subject | benzo[a]pyrene | - |
| dc.subject | colorectal cancer | - |
| dc.subject | chemoprevention | - |
| dc.subject | gut microbiota | - |
| dc.title | 白皮杉醇對苯駢芘/葡聚醣硫酸鈉誘導的小鼠結腸炎相關結直腸癌的化學預防功效和分子機制 | zh_TW |
| dc.title | Chemopreventive efficacy and molecular mechanisms of piceatannol on benzo[a]pyrene/dextran sodium sulfate induced colitis-associated colorectal cancer development in mice | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 114-1 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 何元順;黃步敏;王應然;郭靜娟;魏宗德;蘇純立;張嘉哲;陳炳輝 | zh_TW |
| dc.contributor.oralexamcommittee | Yuan-Soon Ho;Bu-Miin Huang;Ying-Jan Wang;Ching-Chuan Kuo;Tzong-Der Way;Chun-Li Su;Chia-Che Chang;Bing-Huei Chen | en |
| dc.subject.keyword | 白皮杉醇,苯駢芘結腸直腸癌癌症化學預防腸道菌相 | zh_TW |
| dc.subject.keyword | piceatannol,benzo[a]pyrenecolorectal cancerchemopreventiongut microbiota | en |
| dc.relation.page | 154 | - |
| dc.identifier.doi | 10.6342/NTU202600561 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2026-02-05 | - |
| dc.contributor.author-college | 生物資源暨農學院 | - |
| dc.contributor.author-dept | 食品科技研究所 | - |
| dc.date.embargo-lift | 2026-02-12 | - |
| 顯示於系所單位： | 食品科技研究所 | |
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