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Understanding the functional role of selected bioactive compounds and altered genes on gastric carcinogenesis of the differentiated subtype using A4gnt-deficient mice model

DESAMERO, MARK JOSEPH MARANAN 東京大学 DOI:10.15083/0002004969

2022.06.22

概要

An emerging frontier in gastric cancer (GC) research has unveiled the role of a defective glycosylation in the gastric gland mucin function. Loss of the O-glycan terminal, α1, 4-linked Nacetylglucosamine residues (αGlcNAc) on the MUC6 scaffold protein has connoted a strong malignant repercussion with differentiated subtype orientation. Similarly in mice, deletion of the glycosyltransferase gene- α1, 4-N-acetylglucosaminyltransferase (gene symbol: A4gnt) was tightly associated with a concomitant abolition of α1GlcNAc expression leading to a well-recapitulated stepwise GC progression. In the present dissertation, I took advantage of this A4gnt knockout (KO) mice model and established whether it could facilitate both bioactivity testing and gene function studies.

In the first chapter, I clarified the efficacy of a brown seaweed-derived soluble-type β-glucan (Laminaran) on the premalignant cancer progression using 12-15 week-old A4gnt KO mice that specifically display low-grade gastric dysplasia. Following three consecutive weeks of treatment, Laminaran caused a marked attenuation of the gross mucosal lesion, which corresponded histologically to a substantial inhibition of the pyloric mucosal thickness and polymorphonuclear lymphocytes (PMNLs) infiltration. Moreover, as opposed to the untreated control group, Laminaran effectively counterbalanced the increased induction in both proliferative and angiogenic processes and modulated the gene transcripts of several inflammation-associated cytokine showing significant restoration of Il10 expression and considerable repression of Il11 gene transcription. These findings altogether indicate that Laminaran can exert a remarkable restraint on the progressive development of gastric dysplasia.

In the second chapter, the preferential utility of the 60-week old A4gnt KO mice that exhibit fullblown differentiated-type GC has assisted crucially in illuminating the antitumor property of the crude ethanolic extract of propolis (EEP) from the Philippine stingless bees (Tetragonula biroi Friese). In this study, I highlighted the first indication of a significant subtype specificity of EEP towards differentiated subtype of GC but not diffuse-type as ascribed from the results derived on five different human gastric cancer cell lines. Mechanistically, this was found to involve a profound modulation of several cell cycle related gene transcripts, which notably correlated with cell cycle arrest at the G0/G1 phase. To reinforce these observations, EEP-treated A4gnt KO mice demonstrated a significant regression of the gross and histological lesions of gastric pyloric tumors in contrast with the corresponding KO control animals. Also, the specific gene expression regulation of selected cell cycle components and the considerable augmentation of p21 protein coupled with the marked reduction of actively dividing S-phase cells irrevocably supported these observations. Together, these findings alluded to the significant tumor suppressive activity of the Philippine stingless bee propolis, which can be potentially exploited as an adjunct therapeutic option in cases of non-invasive differentiated-type GC.

Lastly for the third chapter, I explored the plausibility of harnessing the capacity of A4gnt KO mice to shed light on the apparent obscurity in the contribution of the gastrointestinal tract-tropic galactose binding lectin, galectin-4 (gene symbol: Lgals4) in gastric carcinogenesis. Here, I initially validated the strong affinity of galectin-4 towards differentiated-type orientation in different established models of GC including canine cases of gastric mucosal lesions, human gastric cancer cell lines, and A4gnt KO mice. A novel A4gnt/Lgals4 double KO (DKO) mouse was subsequently generated to comprehensively ascertain the stage-specific in vivo action of galectin-4. As clearly shown by the combined morphological and gene expression analyses, these DKO mice exemplified two distinct phenotypic traits. At 10- and 30 weeks of age, the relative increase in pyloric mucosal thickness was accompanied by a heightened proliferative and angiogenic processes and upregulated transcription of few pro-inflammatory cytokines and chemokine ligands. Contrastingly, at 50-week old, these DKO mice exemplified a profound tumor growth restriction, depressed proliferation and angiogenesis, and down-expressed gene expression of pro-inflammatory cytokines and chemokines. Interestingly, irrespective of the age (or cancer stage), the magnitude of the distribution of the infiltrating T-lymphocytes and macrophages in the A4gnt/Lgals4 DKO animals were significantly dampened as opposed to those of the A4gnt KO counterpart. Furthermore, using an additional novel model, A4gnt/Il11 DKO and A4gnt/Lgals4/Il11 triple KO (TKO) mice, I later proposed that in these 50-week old A4gnt/Lgals4 DKO mice, IL-11/STAT3 signaling appeared to be a critical regulatory pathway as divulged by the profound decrement in the phosphorylated-STAT3 (P-STAT3) profile and the pronounced improvement in all the above-mentioned parameters in comparison with the corresponding A4gnt KO control.

Based on the account of these above-mentioned studies, the two-fold objective of (1) probing the efficacy of selected bioactive compounds and (2) delimiting the function of an altered genes in GC was greatly realized following the conscious decision to employ this unique A4gnt KO mice. Truly, the utility of this in vivo animal model served as a powerful tool in acquiring a more holistic view of GC and in advancing the field of biomedical science.

参考文献

Abbas, T. & Dutta, A. p21 in cancer: Intricate networks and multiple activities. Nat. Rev. Cancer 9. 400-414, doi: 10.1038/nrc2657 (2009).

Akama, Y., Yasui, W., Kuniyasu, H., Yokozaki, H., Akagi, M., Tahara, H., Ishikawa, T. & Tahara, E. Genetic status and expression of the cyclin-dependent kinase inhibitors in human gastric carcinoma cell lines. Jpn. J. Cancer. Res. 87. 824-830 (1996).

Akao, Y., Maruyama, H., Matsumoto, K., Ohguchi, K., Nishizawa, K., Sakamoto, T.,

Araki, Y., Mishima, S. & Nozawa, N. Cell growth inhibitory effect of cinnamic acid derivatives from propolis on human tumor cell lines. Biol. Pharm. Bull. 26. 1057-1059 (2003).

Alizadeh, A.M., Afrouzan, H., Dinparast-Djadid, N., Sawaya, A.C.H.F., Azizian, S., Hemmati, H.R., Mohagheghi, M.A. & Erfani, S. Chemoprotection of MNNG-initiated gastric cancer in rats using Iranian propolis. Arach. Iran. Med. 18. 18-23 (2015).

Alvarez, P.L.J., Cruz, M.B., Micor, J.R.L., Fajardo Jr., A.C., Cervancia, C.R. & Hizon-Fradejas, A. Identification of flavonoids and phenolic compounds in propolis from stingless bees (Tetragonula biroi Friese) nests and extracts from five sources using tandem liquid chromatography-mass spectrometry. Philipp Ent. 27. 91-99 (2013).

Amini-Sarteshnizi, N., Mobini-Dehkordi, M., Khosravi-Farsani, S. & Teimori, H. Anticancer activity of ethanolic extract of propolis on AGS cell line. J. HerbMed Pharmacol. 4. 29-34 (2015).

Avital, I., Nissan, A., Golan, T., Lawrence, Y.R. & Stojadinovic. Cancer of the stomach. In: DeVita Jr. V.T., Lawrence, T.S. & Rosenberg, S.A. Cancer principles and practice of oncology. 11th edition. Philadelphia: Wolters Kluwer, 2019; 762-802.

Bang, Y-J., Cutsem, E.V., Feyereislova, A., Chung, H.C., Shen, L., Sawaki, A., Lordick, F., Ohtsu, A., Omuro, Y., Satoh, T., Aprile, G., Kulikov, E., Hill, J., Lehle, M., Ruschoff, J. & Kang, Y-K. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet 317. 687- 697, doi: 10.1016/S0140-6736(10)61121-X (2010).

Bankova V. Chemical diversity of propolis and the problem of stardardization. J. Ethnopharmacol. 100. 114-117, doi: 10.1016/j.jep.2005.05.004 (2005).

Baranoski, A., Oliveira, M.T., Semprebon, S.C., Niwa, A.M., Ribeiro, L.R. & Mantovani, M.S. Effects of sulfated and non-sulfated β-glucan extracted from Agaricus brasiliensis in breast adenocarcinoma cells- MCF7. Toxicol. Mech. Methods. 25. 672-679 (2015).

Barsanti, L., Passarelli, V., Evangelista, V., Frassanito, A.M. & Gualtieri, P. Chemistry, physico-chemistry and applications linked to biological activities of β-glucans. Nat. Prod. Rep. 28. 457-466 (2011).

Bartsch, H. & Nair, J. Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: role of lipid peroxidation, DNA damage, and repair. Langenbecks Arch Surg. 391. 499-510 (2006).

Bayram, S., Bayram, N.E., Gercek, Y.C., Aydogan, M.N. & Oz, G.C. Chemical analysis and antimicrobial effect of propolis from Hakkari province of Turkey against some pathogenic microorganisms. Eur. J. Biol. 76. 74-78, doi: 10.5152/EurJBiol.2017.1713 (2017).

Berg, D.J., Lynch, N.A., Lynch, R.G. & Lauricella, D.M. Rapid development of severe hyperplastic gastritis with gastric epithelial dedifferentiation in Helicobacter felisinfected IL-10-/- mice. Am. J. Pathol. 152. 1377-1386 (1998).

Besson, A., Dowdy, S.F., & Roberts, J.M. CDK inhibitors: Cell cycle regulators and beyond. Dev. Cell 14. 159-169, doi: 10.1016/j.devcel.2008.01.013 (2008).

Bijlsma, M.F., Sadanandam, A., Tan, P. & Vermeulen, L. Molecular subtypes in cancer of the gastrointestinal tract. Nature Rev. Gastroenterol. Hepatol. doi: 10.1038/nrgastro.2017.33 (2017).

Bonvehi, J.S. & Coll, F.V. Phenolic composition of propolis from China and from South America. Z. Naturforsch. 49c. 712-718 (1994).

Borrmann, R. Geschwulste des magens and duodenums. In: Henke, F., Lubarsch, O. (eds.). Handbuch der speziellen pathologischen anatomie and histologie. Berlin: SpringerVerlag, 1926; 865.

Boussioutas, A., Li, H., Liu, J., Waring, P., Lade, S., Holloway, A.J., Taupin, D., Gorringe, K., Haviv, I., Desmond, P.V. & Bowtell, D.D.L. Distinctive patterns of gene expression in premalignant gastric mucosa and gastric cancer. Cancer Res. 63. 2569-2577 (2003).

Bray, F., Ferlay, J. Soerjomataram, I., Siegel, R.L., Torre, L.A. & Jemal, A. Global cancer statistics: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68. 394-424, doi: 10.3322/caac.21492 (2018).

Brihoum, H., Maiza, M., Sahali, H., Boulmeltout, M., Barratt, G., Benguedouar, L. & Lahouel, M. Dual effect of Algerian propolis on lung cancer: Anti-tumor and chemoproventive effects involving antioxidant activity. Braz. J. Pharm. Sci. 54. e17396, doi: http://dx.doi.org/10.1590/s2175-97902018000117396 (2018).

Brown, G.D. & Gordon, S. A new receptor for β-glucans. Nature. 413. 36-37 (2001).

Cai, X., Carlson, J., Stoicov, C., Li, H., Wang, T.C., Houghton, J. Helicobacter felis eradication restores normal architecture and inhibits gastric cancer progression in C57BL/6J mice. Gastroenterol. 128. 1937-1952 (2005).

Calhelha, R.C., Falcão, S., Queiroz, M.J.R.P., Vilas-Boas, M. & Ferreira, I.C.F.R. Cytotoxicity of Portuguese propolis: The proximity of the in vitro doses for tumor and normal cell lines. Biomed Res. Int. Article ID 897361, 7 pages, doi: http://dx.doi.org/10.1155/2014/897361 (2014).

Cancer Genome Atlas Research Network: Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 513. 202-209, doi: 10.1038/nature13480 (2014).

Carneiro, F., Seixas, M., Sobrinho-Simoes M. New elements for an updated classification of the carcinomas of the stomach. Pathol. Res. Pract. 191. 571-584, doi: 10.1016/s0344-0388(11)80878-2 (1995).

Carneiro, F. & Lauwers, G.Y. Epithelial tumours of the stomach. In: Shepherd, N.A., Warren, B.F., Williams, G.T., Greenson, J.K., Lauwers, G.Y. & Novelli, M.R. Morson and Dawson’s Gastrointestinal Pathology. Fifth Edition. UK: Wiley-Blackwell, 2013;180-209.

Carrasco, V., Canfran, S., Rodriguez-Franco, F., Benito, A., Sainz, A. & RodriguezBertos A. Canine gastric carcinoma: immunohistochemical expression of cell cycle proteins (p53, p21, and p16) and heat shock proteins(Hsp27 and Hsp70). Vet. Pathol. 48. 322-329 (2011).

Catchpole, O., Mitchell, K., Bloor, S., Davis, P. & Suddes, A. Antiproliferative activity of New Zealand propolis and phenolic compounds vs human colorectal adenocarcinoma cells. Fitoterapia 106. 167-174, doi: http://dx.doi.org/10/1016/j.fitote.2015.09.004 (2015).

Celińska-Janowicz, K., Zareba, I., Lazarek, U., Teul, J., Tomczyk, M., Palka, J. & Miltyk, W. Constituents of propolis: Chrysin, caffeic acid, p-coumaric acid, and ferulic acid induce PRODH/POX-dependent apoptosis in human tongue squamous cell carcinoma cell (CAL-27). Front. Pharmacol. 9. 336, doi: 10.3389/fphar.2018.00336 (2018).

Cervancia, C.R., de Guzman, L.I., Polintan, E.A., Dupo, A.L.B. & Locsin, A.A.

Current status of small hive beetle infestation in the Philippines. J. Apic. Res. doi: 10.1080/00218839.2016.1194053 (2016).

Chen, X., Leung, S.Y., Yuen, S.T., Chu, K- M., Ji, J., Li, R., Chan, A.S.Y., Law, S., Troyanskaya, O.G., Wong, J., So, S., Botstein, D. & Brown, P.O. Variation in gene expression patterns in human gastric cancers. Mol. Biol. Cell. 14. 3208-3215, doi: 10.1091/mbc.E02-12-0833 (2003).

Chen, C-N., Wu, C-L. & Lin, J-K. Apoptosis of human melanoma cells induced by the novel compounds propolin A and propolin B from Taiwanese propolis. Cancer Lett. 245. 218-231, doi: 10.1016/j.canlet.2006.01.016 (2007).

Collins, K.J., Fitzgerald, G.F., Stanton, C. & Ross, R.P. Looking beyond the terrestrial: the potential of seaweed derived bioactive to treat non-communicable diseases. Mar. Drugs. 14. 60, doi: 10.3390/md14030060 (2016).

Cooper, J.P., & Youle, R.J. Balancing cell growth and death. Curr. Opin. Cell Biol. 24. 802-803 (2012).

Correa, P. & Piazuelo, M.B. The gastric precancerous cascade. J. Dig. Dis. 13. 2-9 (2012).

Coussens, L.M. & Werb, Z. Inflammation and cancer. Nature. 420. 860-867 (2002).

Cristescu, R., Lee, J., Nebozhyn, M., Kim, K-M., Ting, J.C., Wong, S.S., Liu, J., Yue, Y.G., Wang, J., Yu, K., Ye, X.S., Do, I-G., Liu, S., Gong, L., Fu, J., Jin, J.G., Choi, M.G., Sohn, T.S., Jung, S-H., Tan, P., Chen, R., Hardwick, J., Kang, W.K., Ayers, M., Hongyue, D., Reinhard, C., Loboda, A., Kim, S. & Aggarwal, A. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 21. 449-456, doi: 10.1038/nm.3850 (2015).

Cunningham, D., Allum, W.H., Stenning, S.P., Thompson, J.N., Van de Velde, C.J.H., Nicolson, M., Scarffe, H., Lofts, F.J., Falk, S.J., Iveson, T.J., Smith, D.B., Langley, R.E., Verma, M., Weeden, S & Chua, W.J. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N. Engl. J. Med. 355. 11-20 (2006).

Da Cunha, M.G. et al. Antimicrobial and antiproliferative activities of stingless bee Melipona scutellaris geopropolis. BMC Complem. Altern. M. 13. 23, doi: http://www.biomedcentral.com/1472-6882/13/23 (2013).

Desamero, M.J.M., Villablanca, M.A., Bariuan, J.V., Collantes, T.M.A., Ang Gobonseng, D.T., Ang, M.J.C., Fajardo, A.C., Cervancia, C.R., Estacio, M.A.C. Honey and propolis abrogate neurologic deficit and neuronal damage in the hippocampus and cerebral cortex of ischemic stroke rats. IJARNP. 10. 7-15 (2017).

Desamero, M.J.M., Kakuta, S., Chambers, J.K., Uchida, K., Hachimura, S., Takamoto, M., Nakayama, J., Nakayama, H & Kyuwa, S. Orally administered brown seaweed-derived β-glucan effectively restrained development of gastric dysplasia in A4gnt KO mice that spontaneously develop gastric adenocarcinoma. Int. Immunopharm. 60. 211- 220, doi: https://doi.org/10.1016/j.intimp.2018.05.002 (2018).

Driscoll, M., Hansen, R., Ding, C., Cramer, D.E. & Yan, J. Therapeutic potential of various β-glucan sources in conjunction with anti-tumor monoclonal antibody in cancer therapy. Cancer Biol. Ther. 8. 218-225 (2009).

El-Khawaga, O-A., Salem, T.A. & Elshal, M.F. Protective role of Egyptian propolis against tumor in mice. Clin. Chim. Acta. 338. 11-16, doi: 10.1016/S0009-8981(03)00323-1 (2003).

Ermakova, S., Men’shova, R., Vishchuk, O., Kim, S.M., Um, B.H., Isakov, V. & Zvyagintseva, T. Water-soluble polysaccharide from the brown alga, Eisenia bicyclis: structural characteristics and antitumor activity. Algal Res. 2. 51-58 (2013).

Ernst, M., Najdovska, M., Grail, D., Lundgren-May, T., Buchert, M., Tye, H., Matthews, V.B., Armes, J., Bhathal, P.S., Hughes, N.R., Marcusson, E.G., Karras, J.G., Na, S., Sedgwick, J.D., Hertzog, P.J. & Jenkins, B.J. STAT3 and STAT1 mediate IL-11- dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice. J. Clin. Invest. 118. 1727-1738 (2008).

Evan, G.I. & Vousden, K. H. Proliferation, cell cycle and apoptosis in cancer. Nature 411. 342-438 (2001).

Ferlay, J., Shin, H-R., Bray, F., Forman, D., Mathers, C. & Parkin, D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer. 127. 2893-2917, doi: 10.1002/ijc.25516 (2010).

Fox, J.G., Beck, P., Dangler, C.A., Whary, M.T., Wang, T.C., Shi, H.N. & NaglerAnderson, C. Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces helicobacter-induced gastric atrophy. Nat. Med. 6. 536-542 (2000).

Franklin, D. S., Godfrey, V.L., O’Brien, D.A., Deng, C. & Xiong, Y. Functional collaboration between different cyclin-dependent kinase inhibitors suppresses tumor growth with distinct tissue specificity. Mol. Cell Biol. 20. 6147-6158 (2000).

Frioń-Herrera, Y., Díaz-Garcia, A., Ruiz-Fuentes, J., Rodríguez-Sánchez, H. & Sforcin, J.M. Mechanism underlying the cytotoxic effect of propolis on human laryngeal epidermoid carcinoma cells. Nat. Prod. Res. 32. 2085-2091, doi: http://doi.org/10.1080/14786419.2017.1363749 (2018).

Goodridge, H.S., Reyes, C.N., Becker, C.A., Katsumoto, T.R., Ma, J., Wolf, A.J., Bose, N., Chan, A.S.H., Magee, A.S., Danielson, M.E., Weiss, A., Vasilakos, J.P. & Underhill, D.M. Activation of the innate immune receptor Dectin-1 upon formation of a “phagocytic synapse”. Nature. 472. 471-475 (2011).

Goseki, N., Takizawa, T., Koike M. Differences in the mode of the extension of the gastric cancer classified by histological type: new histological classification of gastric carcinoma. Gut. 33. 606-612 (1992).

Grivennikov, S.I., Greten, F.R. & Karin, M. Immunity, inflammation, and cancer. Cell 140. 883-899 (2010).

Gulmen, S., Kiris, I., Kocyigit, A., Dogus, D.K. & Ceylan, B.G. Meteoglu, β-glucan protects against lung injury induced by abdominal aortic ischemia-reperfusion in rats. J. Surg. Res. 164. e325-e332 (2010).

Harvey, A.L., Edrada-Ebel, R. & Quinn, R.J. The re-emergence of natural products for drug discovery in the genomics era. Nat. Rev. Drug Discov. 14. 111-129, doi: 10.1038/nrd4510 (2015).

Hasler, C.M. Functional foods: benefits, concerns and challenges – a position paper from the American council of science and health. J. Nutr. 132. 3772-3781 (2002).

Hayakawa, Y., Fox, J.G., Gonda, T., Worthley, D.L., Muthupalani, S. & Wang, T.C. Mouse models of gastric cancer. Cancers. 5. 92-130, doi: 10.3390/cancers5010092 (2002). Hazama, S., Watanabe, S., Ohashi, M., Yagi, M., Suzuki, M., Matsuda, K., Yamamoto, T., Suga, Y., Suga, T., Nakazawa, S. & Oka, M. Efficacy of orally administered superfine dispersed lentinan (β-1, 3-Glucan) for the treatment of advanced colorectal cancer. Anticancer Res. 29. 2611-2618 (2009).

He, G., Siddik, Z.H., Huang, Z., Wang, R., Koomen, J., Kobayashi, . Induction of p21 by p53 following DNA damage inhibits Cdk4 and Cdk2 activities. Oncogene 24, 2929-2943 (2005).

Helicobacter and cancer collaborative group. Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut. 49. 347-353 (2001).

Herre, J., Marshall, A.S.J., Caron, E., Edwards, A.D., Williams, D.L., Schweighoffer, E., Tybulewicz, V., Sousa, C.R., Gordon, S. & Brown, G.D. Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages. Blood. 104. 4038-4045 (2004).

Hoffman, R., Paper, D.H., Donaldson, J. & Vogl, H. Inhibition of angiogenesis in murine tumour growth by Laminaran sulphate. Br. J. Cancer. 73. 1183-1186 (1996).

Hong, F., Yan, J., Baran, J.T., Allendorf, D.J., Hansen, R.D., Ostroff, G.R., Xing, P.X., Cheung, N.-K.V. & Ross, G.D. Mechanism by which orally administered of β-1,3- glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models. J. Immunol. 173. 797-806 (2004).

Hong, H., Kim, C.J., Kim, J.D. & Seo, J.H. β-glucan reduces exercise-induced stress through downregulation of c-Fos and c-Jun expression in the brains of exhausted rats. Mol. Med. Rep. 9. 1660-1666 (2014).

Hu, B., El Hajj, N., Sittler, S., Lammert, N., Barnes, R. & Meloni-Ehrig, A. Gastric cancer: classification, histology and application of molecular pathology. J. Gastrointest. Oncol. 3. 251-261, doi: 10.3978/j.issn.2078-6891.2012.021, (2012).

Hugen, S., Thomas, R.E., German, A.J., Burgener, I.A. & Mandiger, P.J.J. Gastric carcinoma in canines and humans, a review. Vet. Comp. Oncol. 15. 692-705, doi: 10.1111/vco. 12249 (2017).

Hunter, T. & Pines, J. Cyclins and cancer ii: Cyclin D and CDK inhibitors come of age. Cell. 79. 573-582 (1994).

IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7- 14 June 1994. Schistosomes, liver flukes and Helicobacter pylori. IARC Monogr. Eval. Carcinog. Risks Hum. 61. 1-241 (1994).

Ida, K., Yamanoi, K., Asaka, S., Takeuchi, H., Miyamoto, T., Shiozawa, T. & Nakayama, J. αGlcNAc and its catalyst α4GnT are diagnostic and prognostic markers in uterine cervical tumor, gastric type. Sci. Rep. 9. 13043, doi: https://doi.org/10.1038/s41598- 019-49376-7.

ILSI. Safety assessment and potential health benefits of food components based on selected scientific criteria. Crit. Rev. Food Sci. Nutr. 39. 203-206 (1999).

Ina, K., Kataoka, T. & Ando, T. The use of Lentinan for treating gastric cancer. Anticancer Agents Med. Chem. 13. 681-688 (2013).

Ishihara, M., Naoi, K., Hashita, M. & Suzui, M. Growth inhibitory activity of ethanolic extracts of Chinese and Brazilian propolis in four human colon carcinoma cell lines. Oncol. Rep. 22. 349-354, doi: 10.3892/or_00000444 (2009).

Iwaya, Y., Hasebe, O., Koide, N., Kitahara, K., Suga, T., Shinji, A., Muraki, T., Yokosawa, S., Yamada, S., Arakura, N., Tanaka, E. & Nakayama, J. Reduced expression of αGlcNAc in Barrett’s oesophagus adjacent to Barrett’s adenocarcinoma- a possible biomarker to predict the malignant potential of Barrett’s esophagus. Histopathol. 64. 536-546 (2014).

Jafaar, Z.M.T., Litchfield, L.M., Ivanova, M.M., Radde, B.N., Al-Rayyan, N. & Klinge, C.M. β-D-glucan inhibits endocrine-resistant breast cancer cell proliferation and alters gene expression. Int. J. Oncol. 44. 1365-1375 (2014).

Jang, B-G. & Kim, W.H. Molecular pathology of gastric carcinoma. Pathobiology. 78. 302-310, doi: 10.1159/000321703 (2011).

Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 14. 101-112, doi: 10.1007/s10120-011-0041-5 (2011).

Jemal, A., Center, M.M., DeSantis, C. & Ward, E.M. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol. Biomarkers Prev. 19. 1893- 1907, doi: 10.1158/1055-9965.EPI-10-0437 (2010).

Jerkovic, I., Marijanovic, Z., Kus, P.M. & Tuberoso, C.I.G. Comprehensive study of Mediterranean (Crotian) propolis peculiarity: Headspace volatiles, anti-Varroa-treatment residue, phenolics and antioxidant properties. Chem. Biodivers. 13. 210-218, doi: 10.1002/cbdv.201500053 (2016).

Jiang, Y. &Yu, Y. Transgenic and gene knockout mice in gastric cancer research. Oncotarget. 8. 3696-3710 (2017).

Kalogeropoulos, N., Konteles, S.J., Troullidou, E., Mourtzinos, I. & Karathanos, V.T. Chemical composition, antioxidant activity and antimicrobial properties of propolis extracts from Greece and Cyprus. Food Chem. 116. 452-461, doi: 10.1016. /j.foodchem.2009.02.060 (2009).

Karasawa, F., Shiota, A., Goso, Y., Kobayashi, M., Sato, Y., Masumoto, J., Fujiwara, M., Yokosawa, S., Muraki, T., Miyagawa, S., Ueda, M., Fukuda, M.N., Fukuda, M., Ishihara,

K., & Nakayama, J. Essential role of gastric gland mucin in preventing gastric cancer in mice. J. Clin. Invest. 122. 923-934, doi: 10.1172/JCI59087 (2012).

Karin, M. Nuclear factor-κB in cancer development and progression. Nature. 441. 431-436 (2006).

Kaškonienė, V., Kaškonas, P., Maruška, A. & Kubilienė, L. Chemometric analysis of volatiles of propolis from different regions using static headspace GC-MS. Cent. Eur. J. Chem. 12. 736-746, doi: 10.2478/s11532-014-0521-7 (2014).

Kawakubo, M., Ito, Y., Okimura, Y., Kobayashi, M., Sakura, K., Kasama, S., Fukuda, M.N., Katsuyama, T. & Nakayama, J. Natural antibiotic function of human gastric mucin against Helicobacter pylori infection. Science. 305. 1003-1006 (2004).

Kim, J.W., Cho, H.R. & Ku, S.K. Efficacy of Polycan, a beta-glucan originated from Aureobasidium pullulans SM-2001, on anterior cruciate ligament transection and partial medial meniscectomy-induced-osteoarthritis rats. J. Microbiol. Biotechnol. 22. 274-282 (2012).

Kotawong, K., Chaijaroenkul, W., Muhamad, P. & Na-Bangchang K. Cytotoxic activities and effects of atractylodin and β-eudesmol on the cell cycle arrest and apoptosis on cholangiocarcinoma cell line. J. Pharmacol. Sci. 136. 51-56, doi: https://doi.org/10/1016/j.jphs.2017.09.033 (2018).

Kustiawan, P.M., Puthong, S., Arung, E.T. & Chanchao, C. In vitro cytotoxicity of Indonesian stingless bee products against human cancer cell lines. Asian Pac. J. Trop. Biomed. 4. 549-556, doi: 10.12980/APJTB.4.2014APJTB-2013-0039 (2014).

Kustiawan, P.M., Phuwapraisirisan, P., Puthong, S., Palaga, T., Arung, E.T. & Chanchao, C. Propolis from the stingless bee Trigona encisa from East Kalimantan, Indonesia, induces in vitro cytotoxicity and apoptosis in cancer. Asian Pac. J. Cancer P. 16. 6581-6589, doi: http://dx.doi.org/10.7314/APJCP.2015.16.15.6581 (2015).

Lamberte, L.E., Cabrera, E.C. & Rivera, W.L. Activity of ethanolic extract of propolis (EEP) as a potential inhibitor of quorum sensing-mediated pigment production in Chromobacterium violaceum and virulence factor production in Pseudomonas aeruginosa. Philipp. Agric. Scientist 94. 14-22 (2011).

Lauren, P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma: an attempt at a histo-clinical classification. Acta. Path. et. Microbiol. Scandinav. 64, 31-49 (1965).

Lauwers, G.Y., Carneiro F., Graham, D.Y. Gastric carcinoma. In: Bowman, F.T., Carneiro F., Hruban, R.H. & Theise, N.D. (eds). Classification of Tumours of the Digestive System. Lyon: IARC Press, 2010: 48.

Lee, C., Lee, H., Hwang, S.Y., Moon, C.M. & Hong, S.N. IL-10 plays a pivotal role in Tamoxifen-induced spasmolytic polypeptide-expressing metaplasia in gastric mucosa. Gut Liver 11. 789-797 (2017).

Lei, Z., Tan, I.B., Das, K., Deng, E., Zouridis, H., Pattison, S., Chua, C., Feng, Z., Guan, Y.K., Ooi, C.H., Ivanova, T., Zhang, S., Lee, M., Wu, J., Ngo, A., Manesh, S., Tan, E., Teh, B.T., So, J.B.Y., Goh, L.K., Boussioutas, A., Lim, T.K.H., Flotow, H., Tan, P & Rozen, S.G. Identification of molecular subtypes of gastric cancer with different responses to PI3- kinase inhibitors and 5-fluorouracil. Gastroenterology. 145. 554-565, doi: http://dx.doi.org/10.1053/j.gastro.2013.05.010 (2013).

Lee, H-L., Lin, C-S., Kao, S-H. & Chou, M-C. Gallic acid induces G1 phase arrest and apoptosis of triple-negative breast cancer cell MDA-MB-231 via p38 mitogen-activated protein kinase/p21/p27 axis. Anti-Cancer Drugs. 28. 1150-1156, doi:10.1097/CAD.0000000000000565 (2017).

Lee, Y.K., Bae, K., Yoo, H-S. & Cho, S-H. Benefit of adjuvant traditional herbal medicine with chemotherapy for resectable gastric cancer. Integr. Cancer Ther. 17. 619-627, doi: 10.1177/1534735417753542 (2018).

Lordick, F. & Janjigian, Y.Y. Clinical impact of tumor biology in the management of gastroesophageal cancer. Nature Rev. Clin. Oncol. 13. 348-360, doi: 10.1038/nrclinonc.2016.15 (2016).

Lu, H., Ouyang, W. & Huang, C. Inflammation, a key event in cancer development.

Mol. Cancer Res. 4. 221-233 (2006). Malfertheirner, P., Sipponen, P., Naumann, M., Moayyedi, P., Mégraud, F., Xiao, SD., Sugano, K. & Nyrén, O. Helicobacter pylori infection has the potential to prevent gastric cancer: a state-of-the-art critique. Am. J. Gastroenterol. 100. 2100-2115, doi: 10.1111/j.1572- 0241-2005.41688.x (2005).

Mannino, M.H., Zhu, Z., Xiao, H., Bai, Q., Wakefield, M.R. & Fang, Y. The paradoxical role of IL-10 in immunity and cancer. Cancer Lett. 367. 103-107 (2015).

Massaro, F.C., Brooks, P.R., Wallace, H.M. & Russell, F.D. Cerumen of Australian stingless bees (Tetragonula carbonaria): gas chromatography- mass spectrometry fingerprints and potential anti-inflammatory properties. Naturwissenschaften 98. 329-337, doi: 10.1007/s00114-011-0770-7 (2011).

Masuda, Y., Inoue, M., Miyata, A., Mizuno, S. & Nanba, H. Maitake β-glucan enhances therapeutic effect and reduces myelosupression and nephrotoxicity of cisplatin in mice. Int. J. Immunopharmacol. 9. 620-626 (2009).

Masuda, Y., Inoue, H., Ohta, H., Miyake, A., Konishi, M. & Nanba, H. Oral administration of soluble β-glucans extracted from Grifola frondosa induces systemic antitumor immune response and decreases immunosuppression in tumor-bearing mice. Int. J. Cancer 133. 108-120 (2013).

Mcdonald, J.S., Smalley, S.R., Benedetti, J., Hundahl, S., Estes, N.C., Stemmermann, G.N., Haller, D.G., Ajani, J.A., Gunderson, L.L., Jessup, J.M. & Martenson, J.A. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N. Engl. J. Med. 345. 725-730 (2001).

Mclean, M.H. & El-Omar, E.M. Genetics of gastric cancer. Nature Rev. Gastroenterol. Hepatol. 11. 664-674, doi: 10.1038/nrgastro.2014.143 (2014).

Melliou, E., Stratis, E. & Chinou, I. Volatile constituents of propolis from various regions of Greece. Food Chem. 103. 375-380, doi: 10.1016/j.foodchem.2006.07.033 (2006).

Menaker, R.J., Sharaf, A.A. & Jones, N.L. Helicobacter pylori infection and gastric cancer: host, bug, environment, or all three?. Current Gastroenterol. Rep. 6. 429-435 (2004).

Men’shova, R.V., Ermakova, S.P., Um, B.H. & Zvyagintseva, T.N. The composition and structural characteristics of the brown alga Eisenia bicyclis. Russ. J. Mar. Biol. 39. 208-213 (2013).

Ming, S.C. Gastric carcinoma: a pathological classification. Cancer. 39. 2475-2384(1977).

Miyahara, R., Niwa, Y., Matsuura, T., Maeda, O., Ando, T., Ohmiya, N., Itoh, A, Hirooka, Y. & Goto, H. Prevalence and prognosis of gastric cancer detected by screening in a large Japanese population: Data from a single institute over 30 years. J. Gastroenterol. Hepatol. 22. 1435-1442, doi: 10.1111/j.1440-1746.2007.04991.x (2007).

Mosser, D.M. & Zhang, X. Interleukin-10: new perspective on an old cytokine. Immunol. Rev. 226. 205-218 (2008).

Motomura, M., Kwon, K.M., Suh, S-J., Lee, Y-C., Kim, Y-K., Lee, I-S., Kim, M-S., Kwon, D.Y., Suzuki, I. & Kim, C.H. Propolis induces cell cycle arrest and apoptosis in human leukemic U937 cells through Bcl-2/Bax regulation. Environ. Toxicol. Pharmacol. 26. 61-67, doi: 10.1016/j.etap.2008.01.008 (2008).

Mulligan, R.M. Histogenesis and biological behavior of gastric carcinoma. In: Pathology Annual. Volume 7. New York: Appleton Century Crofts, 1972: 349.

Nakashima, A., Yamada, K., Iwata, O., Sugimoto, R., Atsuji, K., Ogawa, T., Ishibashi-Ohgo, N. & Suzuki, K. β-glucans in foods and its physiological functions. J. Nutr. Sci. Vitaminol. 64. 8-17 (2018).

Nakayama J., Yeh J-C., Misra, A.K. Ito, S., Katsuyama, T. & Fukuda, M. Expression cloning of a human α-1,4-N-acetylglucosaminyltransferase that forms GlcNAcα1→4Galβ→R, a glycan specifically expressed in gastric gland mucous cell-type mucin. Proc. Nat. Acad. Sci. U. S. A. 96. 8991-8996 (1999).

Noureddine, H., Hage-Sleiman, R., Wehbi, B., Fayyad-Kazan, H., Hayar, S., Traboulssi, M., Alyamani, O.A., Faour, W.H. & ElMakhour, Y. Chemical characterization and cytotoxic activity evaluation of Lebanese propolis. Biomed. Pharmacother. 95. 298-307, doi: http://dx.doi.org/10.1016/j.biopha.2017.08.067 (2017).

Novak, M. & Vetvicka, V. β-glucans, history, and the present: immunomodulatory aspects and mechanisms of action. J. Immunotoxicol. 5. 47-57 (2008).

Oršolić, N., Terzić, S., Mihaljević, Ž., Šver, L. & Bašić, I. Effects of local administration of propolis and its polyphenolic compounds on tumor formation and growth. Biol. Pharm. Bull. 28. 1928-1933 (2005).

Pan, M-H., Chang, Y-H., Badmaev, V., Nagabhushanam, K. & Ho, C-T. Pterostilbene induces apoptosis and cell cycle arrest in human gastric cancer cell lines. J. Agric. Food Chem. 55. 7777-7785 (2007).

Park, C.H., Lee, J.G., Lee, A-R., Eun, C.S. & Han, D.S. Network construction of gastric microbiome and organization of microbiome modules associated with gastric carcinogenesis. Sci. Rep. 9. 12444, doi: https://doi.org/10.1038/s41598-019-48925-4 (2019).

Pereira-Filho, R.N., Batista, F.S., Ribeiro, D.R., de Melo, G.C., Reis, F.R., de Melo, A.U.C., Gomes, M.Z., Cardoso, J.C. & Albuquerque Junior, R.L.C. Chemopreventive effect of Brazilian green propolis on experimental dermal carcinogenesis in murine model. Int. J. Morphol. 32. 522-530 (2014).

Pitulescu, M.E., & Adams, R.H. Eph/ephrin molecules—a hub for signaling and endocytosis. Genes Dev. 24. 2480-2492 (2010).

Poh, A.R., O’Donoghue, R.J.J., Ernst, M. & Putoczki, T.L. Mouse models of gastric cancer: matching models to biological questions. Gastroenterol Hepatol. 31. 1257-1272, doi: 10.1111/jgh.13297 (2016). Ohya, A., Yamanoi, K., Shimojo, H., Fujii, C. & Nakayama, J. Gastric gland mucinspecific O-glycan expression decreases with tumor progression from precursor lesions to pancreatic cancer. Cancer Sci. 108. 1897-1902 (2017).

Qiu, M-Z., Cai, M-Y., Zhang, D-S., Wang, Z-Q., Wang, D-S., Li, Y-H. & Xu, R-H. Clinicopathological characteristics and prognostic analysis of lauren classification in gastric adenocarcinoma in China. J. Transl. Med. 11. 58, doi: 10.1186/1479-5876-11-58 (2013).

Ragasa, C.Y., Galian, R.A.F., Ebajo Jr., V.D., Aguda, R.M., Cervancia, C.R. & Shen, C.C. Propolins and glyasperin A from stingless bee nests. Rev. Bras. Farmacogn. 25. 177- 179, doi: http://dx.doi.org/10.1016/j.bjp.2015.03.006 (2015).

Ribeiro-Junior, J.A. et al. Gastroprotective effect of geopropolis from Melipona scutellaris is dependent on production of nitric oxide and prostaglandin. J. Evid. Based Complementary Altern. Med. Article ID459846, 5 pages, doi: http://dx.doi.org/10.1155/2015/459846 (2015).

Rice, P.J., Adams, E.L., Ozment-Skelton, T., Gonzalez, A.J., Goldman, M.P., Lockhart, B.E., Barker, L.A., Breuel, K.F., DePonti, W.K., Kalbfleisch, J.H., Ensley, H.E., Brown, G.D., Gordon, S. & Williams, D.L. Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge. J. Pharmacol. Exp. Ther. 314. 1079-1086 (2005).

Ruthes, A.C., Carbonero, E.R., Córdova, M.M., Baggio, C.H., Santos, A.R.S.,Sassaki, G.L., Cipriani, T.R., Gorin, P.A.J. & Iacomini, M. Lactarius rufus (1→3), (1→6)-βD-glucans: structure, antinociceptive and anti-inflammatory effects. Carbohydr. Polym. 94. 129-136 (2013).

Sakuramoto, S., Sasako, M., Yamaguchi, T., Kinoshita, T., Fujii, M., Nashimoto, A., Furukawa, H., Nakajima, T., Ohashi, Y., Imamura, H., Higashino, M., Yamamura, Y., Kurita, A. & Arai, K. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N. Engl. J. Med. 357. 1810-1820 (2007).

Samuelsen, A.B.C., Schrezenmeir, J. & Knutsen, S.V. Effects of orally administered yeast-derived beta-glucans: a review. Mol. Nutr. Food Res. 58. 183-193 (2014).

Sanches, M.A., Pereira, A.M.S. & Serrão, J.E. Pharmacological actions of extracts of propolis of stingless bees (meliponini). J. Apic. Res. 56, 50-57, doi: https//doi.org/10.108/00218839.2016.1260856 (2017).

Sandvik, A., Wang, Y.Y., Morton, H.C., Aasen, A.O., Wang, J.E. & Johansen, F.E. Oral and systemic administration of β-glucan protects against lipopolysaccharide-induced shock and organ injury in rats. Clin. Exp. Immunol. 148. 168-177 (2007).

Sawaya, A.C.H.F. Composition and antioxidant activity of propolis from three species of Scaptotrigona stingless bees. Food Chem. Toxicol. 1. 37-42, doi: 10.3896/IBRA.4.01.2.03(2009).

Seim-Wikse, T., Kolbjornsen, O., Jorundsson, E., Benestad, S.L., Bjornvad, C.R., Grotmol, T., Kristensen, A.T & Skancke, E. Tumour gastrin expression and serum gastrin concentration in dogs with gastric carcinoma are poor diagnostic indicators. J. Comp. Path. 151. 207-211 (2014).

Sforcin, J.M. & Bankova, V. Propolis: Is there a potential for the development of new drugs? J. Ethnopharmacol. 133. 253-260, doi: 10.1016/ j.jep.2010.10.032 (2010).

Shen, R.L., Wang, Z., Dong, J.L., Xiang, Q.S. & Liu, Y.Q. Effects of oat soluble and insoluble β-glucan on 1,2-dimethylhydrazine-induced early colon carcinogenesis in mice. Food Agric. Immunol. 27. 657-666 (2016).

Shimizu, K., Das, S.K., Hashimoto, T., Sowa, Y., Yoshida, T., Sakai, T., Matsuura, Y. & Kanazawa, K. Arterpillin C in Brazilian propolis induces G0/G1 arrest via stimulation of Cip1/p21 expression in human colon cancer cells. Mol. Carcinog. 44. 93-299, doi: 10.1002/mc.20148 (2014).

Shiratsu, K., Higuchi, K. & Nakayama, J. Loss of gastric gland mucin-specific Oglycans is associated with progression of differentiated-type adenocarcinoma of the stomach, Cancer Sci. 105. 126-133 (2014).

Silva-Carvalho, R., Baltazar, F. & Almeida-Aguiar, C. Propolis: A complex natural product with plethora of biological activities that can be explored for drug development. J. Evid. Based Complementary Altern. Med. Article ID 206439, 29 pages, doi: http//dx.doi.org/10.1115/2015/20649 (2015).

Sitarz, R., Skierucha, M., Mielko, J., Offerhaus, G.J.A., Maciejewski, R. & Polkowski, W.P. Gastric Cancer: epidemiology, prevention, classification, and treatment. Cancer Manag. Res. 10. 239-248 (2018).

Smiderle, F.R., Olsen, L.M., Carbonero, E.R., Baggio, C.H., Freitas, C.S., Marcon, R., Santos, A.R.S., Gorin, P.A.J. & Iacomini, M. Anti-inflammatory and analgesic properties in a rodent model of a (1→3), (1→6)-linked β-glucan isolated from Pleurotus pulmonarius. Eur. J. Pharmacol. 597. 86-91 (2008).

Staton, C.A., Chetwood, A.S.A., Cameron, L.C., Cross, S.S., Brown, N.J. & Reed, M.W.R. The angiogenic switch occurs at the adenoma stage of the adenoma-carcinoma sequence in colorectal cancer. Gut. 56. 1426-1432 (2007).

Sulaiman, G.M., Ad’hiah, A.H., Al-Sammarrae, K.W., Bagnati, R., Frapolli, R., Bello, E., Uboldi, S., Romano, M., Panini, N., Scanziani, E., Pezzolato, M., Erba, E. & D’Incalci, M. Assessing the anti-tumour properties of Iraqi propolis in vitro and in vivo. Food Chem. Toxicol. 50. 1632-1641, doi: 10.1016/j.fct.2012.01.022 (2012).

Swidergall, M., Solis, N.V., Lionakis, M.S. & Filler, S.G. EphA2 is an epithelial cells pattern recognition receptor for fungal β-glucans. Nat. Microbiol. 3. 53-61 (2018).

Takasu, S., Tsukamoto, T., Cao, X.Y., Toyoda, T., Hirata, A., Ban, H., Yamamoto, M., Sakai, H., Yanai, T., Masegi, T., Oshima, M. & Tatematsu, M. Roles of cyclooxygenase2 and microsomal prostaglandin E synthase-1 expression and beta-catenin activation in gastric carcinogenesisin N-methyl-N-nitrosourea-treated K19-C2mE transgenic mice. Cancer Sci. 99. 2356-2364 (2008).

Tan, I.B., Ivanova, T., Lim, K.H., Ong, C.W., Deng, N., Lee, J., Tan, S.H., Wu, J., Lee, M.H., Ooi, C.H., Rha, S.Y., Wong, W.K., Boussioutas, A., Yeoh, K.G., So, J., Wong, W.P., Tsuburaya, A., Grabsch, H., Toh, H.C., Rozen, S., Cheong, J.H., Noh, S.H., Wat, W.K., Ajani, A.J., Lee, J-S., Tellez, M.S. & Tan, P. Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy. Gastroenterology 141. 476-485, doi: 10.1053/j.gastro.2011.04.042 (2011).

Tan, P. & Yeoh, K-G. Genetics and molecular pathogenesis of gastric adenocarcinoma. Gastroenterology. 149. 1153-1162, doi: http://dx.doi.org/10.1053/j.gastro.2015.05.059 (2015).

Tanaka, K.I., Tanaka, Y., Suzuki, T. & Mizushima, T. Protective effects of β- (1,3→1,6)-D-glucan against irritant-induced gastric lesions. Br. J. Nutr. 106. 475-485 (2011).

Tang, C., Kamiya, T., Liu, Y., Kadoki, M., Kakuta, S., Oshima, K., Hattori, M., Takeshita, K., Kanai, T., Saijo, S., Ohno, N. & Iwakura, Y. Inhibition of dectin-1 signaling ameliorates colitis by inducing Lactobacillus-mediated regulatory T cell expansion in the intestine. Cell Host Microbe 18. 183-197 (2015).

Tang, H., Yao, X., Yao, C., Zhao, X., Zuo, H. & Li, Z. Anti-colon cancer effect of caffeic acid p-nitro-phenethyl ester in vitro and in vivo and detection of its metabolites. Sci. Rep. 7. 7599, doi: 10.1038/s41598-017-07953-8 (2017).

Tanikawa, T., Wilke, C.M., Kryczek, I., Chen, G.Y., Kao, J., Núñes, G. & Zou, W. Interleukin-10 ablation promotes tumor development, growth, and metastasis. Cancer Res. 72. 420-429 (2012).

Tay, S.T., Leong, S.H., Yu, K., Aggarwal, A., Tan, S.Y., Lee, C.H., Wong, K., Visvanathan, J., Lim, D., Wong, W.K., Soo, K.C., Kon, O.L. & Tan, P. A combined comparative genomic hybridization and expression microarray analysis of gastric cancer reveals novel molecular subtypes. Cancer Res. 63. 3309-3316 (2003).

Teerasripreecha, D., Phuwapraisirisan, P., Puthong, S., Kimura, K., Okuyama, M., Mori, H., Kimura, A. & Chanchao, C. In vitro antiproliferative/cytotoxic activity on cancer cell lines of a cardanol and a cardol enriched from Thai Apis mellifera propolis. BMC Complem. Altern. M. 12. 27, doi: http://www.biomedcentral.com/1472-6882/12/27 (2012).

Thrumurthy, S.G., Chaudry, M.A., Chau, I. & Allum, W. Does surgery have a role in managing incurable gastric cancer? Nat. Rev.Clin. Oncol. 12. 676-682 (2015).

Tsukada, C., Yokoyama, H., Miyaji, C., Ishimoto, Y., Kawamura, H. & Abo, T. Immunopotentiation of intraepithelial lymphocytes in the intestine by oral administrations of β-glucan. Cell. Immunol. 221. 1-5 (2003).

Tsukamoto, T., Tsutomu, M. & Tatematsu, M. Animal models of gastric carcinogenesis. Toxicol. Pathol. 35. 636-648, doi: 10.1080/01926230701420632 (2007).

Umthong, S., Phuwapraisirisan, P., Puthong, S. & Chanchao, C. In vitro antiproliferative activity of partially purified Trigona laeviceps propolis from Thailand on human cancer cell lines. BMC Complem. Altern. M. 11. 37, doi: http://www.biomedcentral.com/1472-6882/11/37 (2011).

Wang, X., Sankarapandian, K., Cheng, Y., Woo, S.O., Kwon, H.W. Perumalsamy, H. & Ahn, Y-J. Relationship between total phenolic contents and biological properties of propolis from 20 different regions in South Korea. BMC Complem. Altern. M. 16. 65, doi: 10.1186/s12906-016-1043-y (2016).

Watabe, M., Hishikawa, K., Takayanagi, A., Shimizu, N. & Nakaki, T. Caffeic acid phenethyl ester induces apoptosis by inhibition of NFκB and activation of Fas in human breast cancer MCF-7 cells. J. Biol. Chem. 279. 6017-6026, doi: 10.1074/jbc.M306040200 (2004).

Weng, M-S., Liao, C-H., Chen, C-N., Wu, C-L. & Lin, J-K. Propolin H from Taiwanese propolis induces G1 arrest in human lung carcinoma cells. J. Agric. Food Chem. 55. 5289-5298, doi: 10.1021/jf070201n (2007).

Wroblewski, L.E., Peek, Jr. R.M., & Wilson, K.T. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin. Microbiol. Rev. 23. 713-739, doi: 10.1128/CMR.00011-10 (2010).

Xu, H., Zou, W., Xu, X. & Zhang, L. Anti-tumor effect of β-glucan from Lentinus edodes and the underlying mechanism. Sci. Rep. 6. 28802 (2016).

Xuan, H., Li, Z., Yan, H., Sang, Q., Wang, K., He, Q., Wang, Y. & Hu, F. Antitumor activity of Chinese propolis in human breast cancer MCF-7 and MDA-MB-231 cells. J. Evid. Based Complementary Altern. Med. Article ID 280120, 11 pages, doi: http/dx.doi.org/10.1155/2014/280120 (2014).

Yamamoto, M., Tsukamoto, T., Sakai, H., Shirai, N., Ohgaki, H., Furihata, C., Donehower, L.A., Yoshida, K. & Tatematsu, M. p53 knockout mice (-/-) are more susceptible than (+/-) and (+/+) mice to N-methyl-N-nitrosourea stomach carcinogenesis. Carcinogenesis. 21. 1891-1897 (2000).

Yamamoto, M., Furihata, C., Ogiu, T., Tsukamoto, T., Inada, K., Hirano, K. & Tatematsu, M. Independent variation in susceptibilities of six different mouse strains to induction of pepsinogen-altered pyloric glands and gastric tumor intestinalization by Nmethyl-N-nitrosourea. Cancer Lett. 179. 121-132 (2002).

Yamamoto, Y., Kimura, T., Sugitachi, A. & Matsuura, N. Anti-angiogenic and antimetastatic effects of β-1,3-D-glucan purified from Hanabiratake, Sparassis crispa. Biol, Pharm. Bull. 32. 259-263 (2009).

Yamanoi, K., Sekine, S., Higuchi, K., Kushima, R. & Nakayama, J. Decreased expression of gastric gland mucin-specific glycan α1,4-linked N-acetylglucosamine on its scaffold mucin 6 is associated with malignant potential of pyloric gland adenoma of the stomach. Histopathol. 67. 898-904 (2015).

Yamanoi, K. & Nakayama, J. Reduced αGlcNAc glycosylation on gastric gland mucin is a biomarker of malignant potential for gastric cancer, Barrett’s adenocarcinoma and pancreatic cancer. Histochem. Cell Biol. 149. 569-575, doi: https://doi.org/10.1007/s00418- 018-1667-8 (2018).

Yan, H., Kakuta, S., Nishihara, M., Sugi, M., Adachi, Y., Ohno, N., Iwakura, Y. & Tsuji, N.M. Kjellmaniella crassifolia Miyabe (gagome) extract modulate intestinal and systemic immune responses. Biosci. Biotechnol. Biochem. 75. 2178-2183 (2011).

Yang, H., Huang, Z., Huang, Y., Dong, W., Pan, Z. & Wang, L. Characterization of Chinese crude propolis by pyrolysis-gas chromatography/mass spectrometry. J. Anal. Appl. Pyrol. 113. 158-164, doi: http://dx.doi.org/10.1016/j.jaap.2014.12.006 (2014).

Yang, X., Zhu, J., Wu, J., Huang, N., Cui, Z., Luo, Y., Sun, F., Pan, Q., Li, Y. & Yang, Q. (-)-Guaiol regulates autophagic cell death depending on mTOR signaling in NSCLC. Cancer Biol. Ther. 19. 706-714, doi: https://doi.org10.1080/15384047.2018.1451277 (2018).

Ye, W., Nyren, O & Adami, H-L. In: Adami, H-O., Hunter, D.J., Lagiou, P. & Mucci, L. (eds). Textbook of Cancer Epidemiology. Third edition. New York: Oxford University Press, 2018: 213-242.

Yu, S., Yang, M. & Nam, K.T. Mouse models of gastric carcinogenesis. J. Gastric Cancer. 14. 67-86, doi: http://dx.doi.org/10.5230/jgc.2014.12.2.67 (2014).

Yuasa, Y. Control of gut differentiation and intestinal-type gastric carcinogenesis. Nat. Rev. Cancer. 3. 592-600, doi: 10.1038/nrc1141 (2003).

Zacchetti, A., Garderen, E.V., Teske, E., Nederbragt, H., Dierendonck, J.H. & Rutteman, D.R. Validation on the use of proliferation markers in canine neoplastic and non- neoplastic tissues: comparison of KI-67 and proliferating nuclear cell antigen (PCNA) expression versus bromodeoxyuridine labeling by immunohistochemistry. APMIS. 111. 430- 438 (2003).

Zheng, H., Takahashi, H., Murai, Y., Cui, Z., Nomoto, K., Miwa, S., Tsuneyama, K. & Takano, Y. Pathobiological characteristics of intestinal and diffuse-type gastric carcinoma in Japan: An immunostaining study on the tissue microarray. J. Clin. Path. 60. 273-277, doi: 10.1136/jcp.2006.038778 (2007).

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