{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T02:34:01Z","timestamp":1778898841600,"version":"3.51.4"},"reference-count":59,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T00:00:00Z","timestamp":1639872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K05879"],"award-info":[{"award-number":["20K05879"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fucoxanthin (Fx) is a marine carotenoid with anti-inflammatory and anti-cancer properties in various animal models of carcinogenesis. However, there is currently no information on the effects of Fx in animal models of pancreatic cancer. We investigated the chemopreventive effects of Fx in C57BL\/6J mice that received allogenic and orthotopic transplantations of cancer cells (KMPC44) derived from a pancreatic cancer murine model (Ptf1aCre\/+; LSL-krasG12D\/+). Using microarray, immunofluorescence, western blot, and siRNA analyses, alterations in cancer-related genes and protein expression were evaluated in pancreatic tumors of Fx-administered mice. Fx administration prevented the adenocarcinoma (ADC) development of pancreatic and parietal peritoneum tissues in a pancreatic cancer murine model, but not the incidence of ADC. Gene and protein expressions showed that the suppression of chemokine (C-C motif) ligand 21 (CCL21)\/chemokine receptor 7 (CCR7) axis, its downstream of Rho A, B- and T-lymphocyte attenuator (BTLA), N-cadherin, \u03b1SMA, pFAK(Tyr397), and pPaxillin(Tyr31) were significantly suppressed in the pancreatic tumors of mice treated with Fx. In addition, Ccr7 knockdown significantly attenuated the growth of KMPC44 cells. These results suggest that Fx is a promising candidate for pancreatic cancer chemoprevention that mediates the suppression of the CCL21\/CCR7 axis, BTLA, tumor microenvironment, epithelial mesenchymal transition, and adhesion.<\/jats:p>","DOI":"10.3390\/ijms222413620","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T20:37:27Z","timestamp":1639946247000},"page":"13620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Fucoxanthin Prevents Pancreatic Tumorigenesis in C57BL\/6J Mice That Received Allogenic and Orthotopic Transplants of Cancer Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"Wataru","family":"Murase","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukino","family":"Kamakura","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serina","family":"Kawakami","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayaka","family":"Yasuda","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Momoka","family":"Wagatsuma","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuhito","family":"Kubota","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Kojima","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan"},{"name":"Advanced Research Promotion Center, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tohru","family":"Ohta","sequence":"additional","affiliation":[{"name":"Advanced Research Promotion Center, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5062-811X","authenticated-orcid":false,"given":"Mami","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Central Animal Division, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michihiro","family":"Mutoh","sequence":"additional","affiliation":[{"name":"Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1428-1582","authenticated-orcid":false,"given":"Takuji","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology and Research Center of Diagnostic Pathology, Gifu Municipal Hospital, Gifu 500-8513, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8546-6250","authenticated-orcid":false,"given":"Hayato","family":"Maeda","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture and Life Science, Hirosaki University, Aomori 036-8561, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Miyashita","sequence":"additional","affiliation":[{"name":"Center for Industry-University Collaboration, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido 080-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1415-5762","authenticated-orcid":false,"given":"Masaru","family":"Terasaki","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan"},{"name":"Advanced Research Promotion Center, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e214708","DOI":"10.1001\/jamanetworkopen.2021.4708","article-title":"Estimated Projection of US Cancer Incidence and Death to 2040","volume":"4","author":"Rahib","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pelosi, E., Castelli, G., and Testa, U. (2017). Pancreatic cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells. Biomedicines, 5.","DOI":"10.3390\/biomedicines5040065"},{"key":"ref_5","unstructured":"American Cancer Society, ACS (2021). Cancer Facts & Figures, American Cancer Society. Available online: cancer.org\/research\/cancer-facts-statistics\/all-cancer-facts-figures\/cancer-facts-figures-2021.html."},{"key":"ref_6","unstructured":"The Cancer Genome Atlas Research Network (2017). Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Cell, 32, 185\u2013203."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nature14169","article-title":"Whole Genomes Redefine the Mutational Landscape of Pancreatic Cancer","volume":"518","author":"Waddell","year":"2015","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6744","DOI":"10.1038\/ncomms7744","article-title":"Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets","volume":"6","author":"Witkiewicz","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1126\/science.1164368","article-title":"Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses","volume":"321","author":"Jones","year":"2008","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cicenas, J., Kvederaviciute, K., Meskinyte, I., Meskinyte-Kausiliene, E., Skeberdyte, A., and Cicenas, J. (2017). KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 Mutations in Pancreatic Cancer. Cancers, 9.","DOI":"10.3390\/cancers9050042"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1053\/j.gastro.2018.08.033","article-title":"Stratification of Pancreatic Ductal Adenocarcinomas Based on Tumor and Microenvironment Features","volume":"155","author":"Puleo","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nature16965","article-title":"Genomic analyses identify molecular subtypes of pancreatic cancer","volume":"531","author":"Bailey","year":"2016","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s10555-021-09982-2","article-title":"The role of microbiome in pancreatic cancer","volume":"40","author":"Li","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S1535-6108(03)00309-X","article-title":"Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse","volume":"4","author":"Hingorani","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1101\/gad.1475506","article-title":"Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression","volume":"20","author":"Ijichi","year":"2006","journal-title":"Genes Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.ccr.2005.04.023","article-title":"Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice","volume":"7","author":"Hingorani","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Terasaki, M., Kubota, A., Kojima, H., Maeda, H., Miyashita, K., Kawagoe, C., Mutoh, M., and Tanaka, T. (2021). Fucoxanthin and Colorectal Cancer Prevention. Cancers, 13.","DOI":"10.3390\/cancers13102379"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tavares, R.S.N., Stuchi Maria-Engler, S., Colepicolo, P., Debonsi, H.M., Sch\u00e4fer-Korting, M., Marx, U., Rigo Gaspar, L., and Zoschke, C. (2020). Skin Irritation Testing Beyond Tissue Viability: Fucoxanthin Effects on Inflammation, Homeostasis, and Metabolism. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12020136"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3358\/shokueishi.52.183","article-title":"Single and 13-week oral toxicity study of fucoxanthin oil from microalgae in rats","volume":"52","author":"Iio","year":"2011","journal-title":"Shokuhin Eiseigaku Zasshi"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"501","DOI":"10.2131\/jts.34.501","article-title":"Single and repeated oral dose toxicity study of fucoxanthin (FX), a marine carotenoid, in mice","volume":"34","author":"Beppu","year":"2009","journal-title":"J. Toxicol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1017\/S0007114511004879","article-title":"Pharmacokinetics of fucoxanthinol in human plasma after the oral administration of kombu extract","volume":"107","author":"Hashimoto","year":"2012","journal-title":"Br. J. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.3945\/jn.110.126466","article-title":"Keto-Carotenoids Are the Major Metabolites of Dietary Lutein and Fucoxanthin in Mouse Tissues","volume":"140","author":"Yonekura","year":"2010","journal-title":"J. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.exer.2005.03.002","article-title":"Effects of fucoxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo","volume":"81","author":"Shiratori","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.abb.2008.09.011","article-title":"Cancer prevention by carotenoids","volume":"483","author":"Nishino","year":"2009","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"108871","DOI":"10.1016\/j.jnutbio.2021.108871","article-title":"Suppression of C-C chemokine receptor 1 is a key regulation for colon cancer chemoprevention in AOM\/DSS mice by fucoxanthin","volume":"99","author":"Terasaki","year":"2022","journal-title":"J. Nutr. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s10565-014-9277-2","article-title":"Inhibitory effects of fucoxanthinol on the viability of human breast cancer cell lines MCF-7 and MDA-MB-231 are correlated with modulation of the NF-kappaB pathway","volume":"30","author":"Rwigemera","year":"2014","journal-title":"Cell Biol. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"407","DOI":"10.21873\/cgp.20268","article-title":"Effect of Fucoxanthinol on Pancreatic Ductal Adenocarcinoma Cells from an N-Nitrosobis(2-Oxopropyl)Amine-Initiated Syrian Golden Hamster Pancreatic Carcinogenesis Model","volume":"18","author":"Terasaki","year":"2021","journal-title":"Cancer Genom. Proteom."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"133","DOI":"10.21873\/cgp.20248","article-title":"A Fucoxanthinol Induces Apoptosis in a Pancreatic Intraepithelial Neoplasia Cell","volume":"18","author":"Terasaki","year":"2021","journal-title":"Cancer Genom. Proteom."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"246","DOI":"10.31989\/ffhd.v7i4.333","article-title":"Seaweed Fucoxanthin Supplementation Improves Obesity Parameters in Mild Obese Japanese Subjects","volume":"7","author":"Hitoe","year":"2017","journal-title":"Funct. Foods Health Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1017\/jns.2017.1","article-title":"Reduction of HbA1c levels by fucoxanthin-enriched akamoku oil possibly involves the thrifty allele of uncoupling protein 1 (UCP1): A randomised controlled trial in normal-weight and obese Japanese adults","volume":"6","author":"Mikami","year":"2017","journal-title":"J. Nutr. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1093\/carcin\/bgaa100","article-title":"Alteration of fecal microbiota by fucoxanthin results in prevention of colorectal cancer in AOM\/DSS-treated mice","volume":"42","author":"Terasaki","year":"2021","journal-title":"Carcinogenesis"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Terasaki, M., Ikuta, M., Kojima, H., Tanaka, T., Maeda, H., Miyashita, K., and Mutoh, M. (2020). Dietary Fucoxanthin Induces Anoikis in Colorectal Adenocarcinoma by Suppressing Integrin Signaling in a Murine Colorectal Cancer Model. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010090"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1073\/pnas.95.1.258","article-title":"A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes","volume":"95","author":"Gunn","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1084\/jem.189.3.451","article-title":"Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization","volume":"189","author":"Gunn","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1159\/000139126","article-title":"Chemokine Receptor CCR7 Expression Correlates with Lymph Node Metastasis in Pancreatic Cancer","volume":"74","author":"Nakata","year":"2008","journal-title":"Oncology"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Xu, Y., Liu, L., Qiu, X., Jiang, L., Huang, B., Li, H., Li, Z., Luo, W., and Wang, E. (2011). CCL21\/CCR7 Promotes G2\/M Phase Progression via the ERK Pathway in Human Non-Small Lung Cancer Cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021119"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"415375","DOI":"10.1155\/2014\/415375","article-title":"CCR7 Regulates Cell Migration and Invasion through JAK2\/STAT3 in Metastatic Squamous Cell Carcinoma of the Head and Neck","volume":"2014","author":"Liu","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_38","first-page":"3282","article-title":"CCR7 enhances the angiogenic capacity of esophageal squamous carcinoma cells in vitro via activation of the NF-\u03baB\/VEGF signaling pathway","volume":"9","author":"Cai","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s13277-015-3819-y","article-title":"CCR7 regulates Twist to induce the epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma","volume":"37","author":"Li","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"849","DOI":"10.3892\/or.2014.3631","article-title":"Chemokine receptor 7 promotes tumor migration and invasiveness via the RhoA\/ROCK pathway in metastatic squamous cell carcinoma of the head and neck","volume":"33","author":"Xu","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1053\/j.gastro.2020.04.037","article-title":"CXCL10 and CCL21 Promote Migration of Pancreatic Cancer Cells Toward Sensory Neurons and Neural Remodeling in Tumors in Mice, Associated with Pain in Patients","volume":"159","author":"Hirth","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"E371","DOI":"10.1002\/ijc.26502","article-title":"Lack of CCR7 expression is rate limiting for lymphatic spread of pancreatic ductal adenocarcinoma","volume":"131","author":"Sperveslage","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhang, L., Wang, D., Li, Y., Liu, Y., Xie, X., Wu, Y., Zhou, Y., Ren, J., Zhang, J., and Zhu, H. (2016). CCL21\/CCR7 Axis Contributed to CD133+ Pancreatic Cancer Stem-Like Cell Metastasis via EMT and Erk\/NF-\u039ab Pathway. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158529"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.3892\/ol.2013.1261","article-title":"Effect of CCR7, CXCR4 and VEGF-C on the lymph node metastasis of human pancreatic ductal adenocarcinoma","volume":"5","author":"Guo","year":"2013","journal-title":"Oncol. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s00534-011-0395-4","article-title":"The chemotactic interaction between CCL21 and its receptor, CCR7, facilitates the progression of pancreatic cancer via induction of angiogenesis and lymphangiogenesis","volume":"18","author":"Zhao","year":"2011","journal-title":"J. Hepatobiliary Pancreat. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/ni944","article-title":"BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1","volume":"4","author":"Watanabe","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e1014246","DOI":"10.1080\/2162402X.2015.1014246","article-title":"BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties","volume":"4","author":"Haymaker","year":"2015","journal-title":"Oncoimmunology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nri1917","article-title":"Balancing co-stimulation and inhibition with BTLA and HVEM","volume":"6","author":"Murphy","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1172\/JCI40070","article-title":"BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination","volume":"120","author":"Rivals","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1186\/s40425-019-0744-4","article-title":"BTLA blockade enhances cancer therapy by inhibiting IL-6\/IL-10-induced CD19high B lymphocytes","volume":"7","author":"Chen","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1111\/cas.12825","article-title":"Clinical significance of tumor-infiltrating immune cells focusing on BTLA and Cbl-b in patients with gallbladder cancer","volume":"106","author":"Oguro","year":"2015","journal-title":"Cancer Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"919","DOI":"10.2147\/OTT.S128825","article-title":"Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis","volume":"10","author":"Lan","year":"2017","journal-title":"OncoTargets Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e1561120","DOI":"10.1080\/2162402X.2018.1561120","article-title":"Prognostic significance of circulating PD-1, PD-L1, pan-BTN3As, BTN3A1 and BTLA in patients with pancreatic adenocarcinoma","volume":"8","author":"Bian","year":"2019","journal-title":"Oncoimmunology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3389\/fmolb.2020.00148","article-title":"Friend or Foe: Prognostic and Immunotherapy Roles of BTLA in Colorectal Cancer","volume":"7","author":"Song","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/00006676-199801000-00003","article-title":"Inhibitory effects of beta-carotene, palm carotene, and green tea polyphenols on pancreatic carcinogenesis initiated by N-nitrosobis(2-oxopropyl)amine in Syrian golden hamsters","volume":"16","author":"Majima","year":"1998","journal-title":"Pancreas"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1093\/carcin\/12.11.2157","article-title":"Inhibitory effects of micronutrients on pancreatic carcinogenesis in azaserine-treated rats","volume":"12","author":"Appel","year":"1991","journal-title":"Carcinogenesis"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.3892\/ol.2015.3809","article-title":"Preventive effects of fermented brown rice and rice bran against N-nitrosobis(2-oxopropyl)amine-induced pancreatic tumorigenesis in male hamsters","volume":"10","author":"Kuno","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1021\/jf3003174","article-title":"Chemopreventive effects of 4-methylthio-3-butenyl isothiocyanate (Raphasatin) but not curcumin against pancreatic carcinogenesis in hamsters","volume":"61","author":"Okamura","year":"2013","journal-title":"J. Agric. Food. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.canlet.2005.10.028","article-title":"Protective effects of benzyl isothiocyanate and sulforaphane but not resveratrol against initiation of pancreatic carcinogenesis in hamsters","volume":"241","author":"Kuroiwa","year":"2006","journal-title":"Cancer Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13620\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:52:06Z","timestamp":1760169126000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,19]]},"references-count":59,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijms222413620"],"URL":"https:\/\/doi.org\/10.3390\/ijms222413620","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,19]]}}}