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研究生(外文):Hui-Chuan Hsu
論文名稱(外文):Inhibitory Effects of Sulindac and Green tea Extract on N-methyl-N-benzylnitrosamine (MBN)-Induced Oral Cancer in Hamster Buccal Pouch
指導教授(外文):Tsung-Yun Liu
外文關鍵詞:NSAIDhamsterbuccal pouchinducegreen tea extractWestern blotimmunohistochemistry
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目前研究顯示口腔癌有cyclooxygenase-2 (COX-2)過度表現的現象,但是COX-2在口腔癌上扮演的角色目前仍不清楚。本研究在測試Sulindac,一個具有化學預防作用的非類固醇抗發炎藥和綠茶萃取物對於由N-methyl-N-benzylnitrosamine (MBN)誘發倉鼠產生口腔癌的抑制作用。先以1% MBN (每週三次)共8週誘發倉鼠產生口腔癌後,再給予含320 ppm sulindac的飼料或含0.2 %的綠茶水共9週,給藥的同時仍持續處理MBN。在給MBN 17週後犧牲倉鼠,結果顯示先誘發口腔癌後再給予藥物的動物模式,Sulindac明顯的抑制腫瘤的數目( p<0.01)及腫瘤的大小(p<0.05),而綠茶萃取物與對照組比較僅抑制了口腔癌的腫瘤數目(p<0.05)。在口腔組織免疫化學試驗,未給MBN對照組的COX-2量很少並且分佈平均,但是在MBN所誘發的鱗狀上皮細胞癌的腫瘤上則有大量的COX-2表現。以西方墨點法來分析COX-2蛋白質的表現,對照組(以 propylene glycol處理),口腔表皮組織COX-2蛋白質的含量非常少幾乎沒有,然而COX-2在鱗狀上皮細胞癌的腫瘤上增加約4倍。結果亦顯示由 MBN誘發產生的鱗狀上皮細胞癌,其組織中PGE2值較對照組明顯增高。綜合以上結果,清楚顯示COX-2與口腔癌發生有關,並且非類固醇抗發炎藥可有效抑制由MBN誘導倉鼠產生口腔鱗狀上皮細胞癌的作用。

Recent studies have demonstrated the overexpression of cyclooxygenase-2 (COX-2) in oral cancer, but the role of COX-2 in oral carcinogenesis remains unclear. This study is designed to test whether sulindac, a potential chemopreventive non-steroidal anti-inflammatory drug (NSAID), and green tea extract has potential to reduce the N-methyl-N-benzylnitrosamine (MBN)-induced tumorigenesis in hamster buccal pouch. Sulindac was administered in the diet (320 ppm) and green tea extract was given in the drinking water (0.2 %) to hamsters that were pretreated with 1 % MBN (3 times a week) for 8 weeks. The sulindac and green tea extract treatment continued for another 9 weeks while the MBN treatment continued. The late treatment of sulindac caused significant reduction in both the multiplicity ( p<0.01) and size ( p<0.05) of tumors than the controls. On the other hand, 0.2% green tea extract in drinking water only reduced the number ( p<0.05) of oral cancer lesions than the controls. By using immunohistochemistry, COX-2 was diffusely stained in control pouch, but strongly present in the MBN-induced tumor cells. Western blot analysis revealed COX-2 protein was barely detectable in the propylene glycol-treated controls, whereas it was increased 4-fold in MBN-induced squamous cell carcinomas (SCCs). The results also indicated the PGE2 level was significantly increased in MBN-induced SCCs than the controls. These results clearly indicate that COX-2 is involved in oral carcinogenesis and NSAID has potential against the postinitiation develeopment of SCCs in MBN-induced hamster oral cancers.

壹、 緒論
第一章 口腔癌
第一節 口腔癌之流行病學
第二節 口腔癌之分子致癌機轉
第三節 口腔癌的治療
第二章 花生四烯酸的代謝
第一節 簡介
第二節 cyclooxygenase的介紹
第三章 COX-2在癌症上扮演的角色
第一節 簡介
第二節 COX-2與大腸癌
第三節 COX-2與口腔癌
第四節 COX-2與其他癌症
第四章 PGE2在癌症上扮演的角色
第五章 Sulindac的介紹
第一節 簡介
第二節 Sulindac與癌症
第六章 綠茶的介紹
第一節 簡介
第二節 綠茶的成分
第三節 綠茶與癌症
第七章 實驗設計
第一節 實驗動物-倉鼠
第二節 MBN的介紹
第三節 實驗模式
貳、 實驗材料
參、 實驗方法
肆、 實驗結果
伍、 討論
陸、 結論
柒、 參考文獻
捌、 實驗圖表

Ahnen, D.J. (1998). Colon cancer prevention by NSAIDs: what is the mechanism of action? Eur J Surg Suppl 111-114.
Alberts, D.S., Hixson, L., Ahnen, D., Bogert, C., Einspahr, J., Paranka, N., Brendel, K., Gross, P.H., Pamukcu, R., and Burt, R.W. (1995). Do NSAIDs exert their colon cancer chemoprevention activities through the inhibition of mucosal prostaglandin synthetase? J Cell Biochem Suppl 22, 18-23.
August, D.A., Landau, J., Caputo, D., Hong, J., Lee, M.J., and Yang, C.S. (1999). Ingestion of green tea rapidly decreases prostaglandin E2 levels in rectal mucosa in humans. Cancer Epidemiol Biomarkers Prev 8, 709-713.
Barch, D.H. and Fox, C.C. (1988). Selective inhibition of methylbenzylnitrosamine-induced formation of esophageal O6-methylguanine by dietary ellagic acid in rats. Cancer Res 48, 7088-7092.
Bauer, A.K., Dwyer-Nield, L.D., and Malkinson, A.M. (2000). High cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) contents in mouse lung tumors. Carcinogenesis 21, 543-550.
Chan, G., Boyle, J.O., Yang, E.K., Zhang, F., Sacks, P.G., Shah, J.P., Edelstein, D., Soslow, R.A., Koki, A.T., Woerner, B.M., Masferrer, J.L., and Dannenberg, A.J. (1999). Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res 59, 991-994.
Chang, K.W., Lin, S.C., Koos, S., Pather, K., and Solt, D. (1996). p53 and Ha-ras mutations in chemically induced hamster buccal pouch carcinomas. Carcinogenesis 17, 595-600.
Chang, K.W., Sarraj, S., Lin, S.C., Tsai, P.I., and Solt, D. (2000). P53 expression, p53 and Ha-ras mutation and telomerase activation during nitrosamine-mediated hamster pouch carcinogenesis. Carcinogenesis 21, 1441-1451.
Chung, F.L. (1999). The prevention of lung cancer induced by a tobacco-specific carcinogen in rodents by green and black tea. Proc Soc Exp Biol Med 220, 244-248.
Coffey, R.J., Hawkey, C.J., Damstrup, L., Graves-Deal, R., Daniel, V.C., Dempsey, P.J., Chinery, R., Kirkland, S.C., DuBois, R.N., Jetton, T.L., and Morrow, J.D. (1997). Epidermal growth factor receptor activation induces nuclear targeting of cyclooxygenase-2, basolateral release of prostaglandins, and mitogenesis in polarizing colon cancer cells. Proc Natl Acad Sci U S A 94, 657-662.
Denkert, C., Kobel, M., Berger, S., Siegert, A., Leclere, A., Trefzer, U., and Hauptmann, S. (2001). Expression of cyclooxygenase 2 in human malignant melanoma. Cancer Res 61, 303-308.
Fischer, S.M., Lo, H.H., Gordon, G.B., Seibert, K., Kelloff, G., Lubet, R.A., and Conti, C.J. (1999). Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesis. Mol Carcinog 25, 231-240.
Fosslien, E. (2000). Biochemistry of cyclooxygenase (COX)-2 inhibitors and molecular pathology of COX-2 in neoplasia. Crit Rev Clin Lab Sci 37, 431-502.
Fosslien, E. (2000). Molecular pathology of cyclooxygenase-2 in neoplasia. Ann Clin Lab Sci 30, 3-21.
Gately, S. (2000). The contributions of cyclooxygenase-2 to tumor angiogenesis. Cancer Metastasis Rev 19, 19-27.
Goldberg, Y., Nassif, I.I., Pittas, A., Tsai, L.L., Dynlacht, B.D., Rigas, B., and Shiff, S.J. (1996). The anti-proliferative effect of sulindac and sulindac sulfide on HT-29 colon cancer cells: alterations in tumor suppressor and cell cycle-regulatory proteins. Oncogene 12, 893-901.
Goluboff, E.T., Shabsigh, A., Saidi, J.A., Weinstein, I.B., Mitra, N., Heitjan, D., Piazza, G.A., Pamukcu, R., Buttyan, R., and Olsson, C.A. (1999). Exisulind (sulindac sulfone) suppresses growth of human prostate cancer in a nude mouse xenograft model by increasing apoptosis. Urology 53, 440-445.
Goodsell, D.S. (2000). The molecular perspective: cyclooxygenase-2. Stem Cells 18, 227-229.
Hawkey, C.J. (1999). COX-2 inhibitors. Lancet 353, 307-314.
Herschman, H.R. (1996). Prostaglandin synthase 2. Biochim Biophys Acta 1299, 125-140.
Hsu, A.L., Ching, T.T., Wang, D.S., Song, X., Rangnekar, V.M., and Chen, C.S. (2000). The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem 275, 11397-11403.
Hull, M.A., Thomson, J.L., and Hawkey, C.J. (1999). Expression of cyclooxygenase 1 and 2 by human gastric endothelial cells. Gut 45, 529-536.
Inaba, A., Uchiyama, T., and Oka, M. (1999). Role of prostaglandin E2 in rat colon carcinoma. Hepatogastroenterology 46, 2347-2351.
Joki, T., Heese, O., Nikas, D.C., Bello, L., Zhang, J., Kraeft, S.K., Seyfried, N.T., Abe, T., Chen, L.B., Carroll, R.S., and Black, P.M. (2000). Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398. Cancer Res 60, 4926-4931.
Kaplan-Machlis, B. and Klostermeyer, B.S. (1999). The cyclooxygenase-2 inhibitors: safety and effectiveness. Ann Pharmacother 33, 979-988.
Katiyar, S.K., Challa, A., McCormick, T.S., Cooper, K.D., and Mukhtar, H. (1999). Prevention of UVB-induced immunosuppression in mice by the green tea polyphenol (-)-epigallocatechin-3-gallate may be associated with alterations in IL-10 and IL-12 production. Carcinogenesis 20, 2117-2124.
Kawamori, T., Rao, C.V., Seibert, K., and Reddy, B.S. (1998). Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 58, 409-412.
Kelloff, G.J., Crowell, J.A., Steele, V.E., Lubet, R.A., Boone, C.W., Malone, W.A., Hawk, E.T., Lieberman, R., Lawrence, J.A., Kopelovich, L., Ali, I., Viner, J.L., and Sigman, C.C. (1999). Progress in cancer chemoprevention. Ann N Y Acad Sci 889, 1-13.
Kelloff, G.J., Hawk, E.T., Crowell, J.A., Boone, C.W., Nayfield, S.G., Perloff, M., Steele, V.E., and Lubet, R.A. (1996). Strategies for identification and clinical evaluation of promising chemopreventive agents. Oncology (Huntingt) 10, 1471-1484.
Kitayama, W., Denda, A., Okajima, E., Tsujiuchi, T., and Konishi, Y. (1999). Increased expression of cyclooxygenase-2 protein in rat urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. Carcinogenesis 20, 2305-2310.
Ko, Y.C., Huang, Y.L., Lee, C.H., Chen, M.J., Lin, L.M., and Tsai, C.C. (1995). Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan. J Oral Pathol Med 24, 450-453.
Kune, G.A. (2000). Colorectal cancer chemoprevention: aspirin, other NSAID and COX-2 inhibitors. Aust N Z J Surg 70, 452-455.
Kune, G.A., Kune, S., and Watson, L.F. (1988). Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res 48, 4399-4404.
Li, M.H., Ji, C., and Cheng, S.J. (1986). Occurrence of nitroso compounds in fungi-contaminated foods: a review. Nutr Cancer 8, 63-69.
Liang, Y.C., Huang, Y.T., Tsai, S.H., Lin-Shiau, S.Y., Chen, C.F., and Lin, J.K. (1999). Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis 20, 1945-1952.
Lin, J.K. and Liang, Y.C. (2000). Cancer chemoprevention by tea polyphenols. Proc Natl Sci Counc Repub China B 24, 1-13.
Loeb, W.F. and Quimby, F.W. (1989). The clinical chemistry of laboratory animals
Lu, Y.P., Lou, Y.R., Li, X.H., Xie, J.G., Brash, D., Huang, M.T., and Conney, A.H. (2000). Stimulatory effect of oral administration of green tea or caffeine on ultraviolet light-induced increases in epidermal wild-type p53, p21(WAF1/CIP1), and apoptotic sunburn cells in SKH-1 mice. Cancer Res 60, 4785-4791.
McAdam, B.F., Catella-Lawson, F., Mardini, I.A., Kapoor, S., Lawson, J.A., and FitzGerald, G.A. (1999). Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci U S A 96, 272-277.
Metz, N., Lobstein, A., Schneider, Y., Gosse, F., Schleiffer, R., Anton, R., and Raul, F. (2000). Suppression of azoxymethane-induced preneoplastic lesions and inhibition of cyclooxygenase-2 activity in the colonic mucosa of rats drinking a crude green tea extract. Nutr Cancer 38, 60-64.
Moore, B.C. and Simmons, D.L. (2000). COX-2 inhibition, apoptosis, and chemoprevention by nonsteroidal anti-inflammatory drugs. Curr Med Chem 7, 1131-1144.
Moore, S.R., Johnson, N.W., Pierce, A.M., and Wilson, D.F. (2000). The epidemiology of tongue cancer: a review of global incidence. Oral Dis 6, 75-84.
Morse, M.A., Kresty, L.A., Steele, V.E., Kelloff, G.J., Boone, C.W., Balentine, D.A., Harbowy, M.E., and Stoner, G.D. (1997). Effects of theaflavins on N-nitrosomethylbenzylamine-induced esophageal tumorigenesis. Nutr Cancer 29, 7-12.
Nagabhushan, M., Ng, Y.K., Elias, R., Polverini, P.J., and Solt, D.B. (1990). Acute inhibition of DNA synthesis in hamster buccal pouch epithelium exposed to indirect acting carcinogens. Cancer Lett 53, 163-173.
Oshima, M., Murai, N., Kargman, S., Arguello, M., Luk, P., Kwong, E., Taketo, M.M., and Evans, J.F. (2001). Chemoprevention of intestinal polyposis in the Apcdelta716 mouse by rofecoxib, a specific cyclooxygenase-2 inhibitor. Cancer Res 61, 1733-1740.
Pentland, A.P., Schoggins, J.W., Scott, G.A., Khan, K.N., and Han, R. (1999). Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis 20, 1939-1944.
Perkins, T.M. and Shklar, G. (1982). Delay in hamster buccal pouch carcinogenesis by aspirin and indomethacin. Oral Surg Oral Med Oral Pathol 53, 170-178.
Piazza, G.A., Rahm, A.L., Krutzsch, M., Sperl, G., Paranka, N.S., Gross, P.H., Brendel, K., Burt, R.W., Alberts, D.S., and Pamukcu, R. (1995). Antineoplastic drugs sulindac sulfide and sulfone inhibit cell growth by inducing apoptosis. Cancer Res 55, 3110-3116.
Qin, G., Gopalan-Kriczky, P., Su, J., Ning, Y., and Lotlikar, P.D. (1997). Inhibition of aflatoxin B1-induced initiation of hepatocarcinogenesis in the rat by green tea. Cancer Lett 112, 149-154.
Rao, C.V., Rivenson, A., Simi, B., Zang, E., Kelloff, G., Steele, V., and Reddy, B.S. (1995). Chemoprevention of colon carcinogenesis by sulindac, a nonsteroidal anti-inflammatory agent. Cancer Res 55, 1464-1472.
Reddy, B.S., Kawamori, T., Lubet, R., Steele, V., Kelloff, G., and Rao, C.V. (1999). Chemopreventive effect of S-methylmethane thiosulfonate and sulindac administered together during the promotion/progression stages of colon carcinogenesis. Carcinogenesis 20, 1645-1648.
Reddy, B.S., Rao, C.V., and Seibert, K. (1996). Evaluation of cyclooxygenase-2 inhibitor for potential chemopreventive properties in colon carcinogenesis. Cancer Res 56, 4566-4569.
Reynolds, N.J., McCombie, S.W., Shankar, B.B., Bishop, W.R., and Fisher, G.J. (1997). SCH 47112, a novel staurosporine derivative, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and epidermal hyperplasia in hairless mouse skin. Arch Dermatol Res 289, 540-546.
Rice, P.L., Goldberg, R.J., Ray, E.C., Driggers, L.J., and Ahnen, D.J. (2001). Inhibition of extracellular signal-regulated kinase 1/2 phosphorylation and induction of apoptosis by sulindac metabolites. Cancer Res 61, 1541-1547.
Rioux, N. and Castonguay, A. (1998). Prevention of NNK-induced lung tumorigenesis in A/J mice by acetylsalicylic acid and NS-398. Cancer Res 58, 5354-5360.
Salley, J.J. (1954). Experimental carcinogenesis in the cheek pouch of the syrian hamster. Dental Res 33, 253-262.
Samaha, H.S., Kelloff, G.J., Steele, V., Rao, C.V., and Reddy, B.S. (1997). Modulation of apoptosis by sulindac, curcumin, phenylethyl-3-methylcaffeate, and 6-phenylhexyl isothiocyanate: apoptotic index as a biomarker in colon cancer chemoprevention and promotion. Cancer Res 57, 1301-1305.
Sato, D. (1999). Inhibition of urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine in rats by green tea. Int J Urol 6, 93-99.
Sawaoka, H., Kawano, S., Tsuji, S., Tsujii, M., Gunawan, E.S., Takei, Y., Nagano, K., and Hori, M. (1998). Cyclooxygenase-2 inhibitors suppress the growth of gastric cancer xenografts via induction of apoptosis in nude mice. Am J Physiol 274, G1061-G1067
Sawaoka, H., Tsuji, S., Tsujii, M., Gunawan, E.S., Sasaki, Y., Kawano, S., and Hori, M. (1999). Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo. Lab Invest 79, 1469-1477.
Scioscia, K.A., Snyderman, C.H., D'Amico, F., Comsa, S., Rueger, R., and Light, B. (2000). Effects of arachidonic acid metabolites in a murine model of squamous cell carcinoma. Head Neck 22, 149-155.
Sheng, H., Shao, J., Kirkland, S.C., Isakson, P., Coffey, R.J., Morrow, J., Beauchamp, R.D., and DuBois, R.N. (1997). Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest 99, 2254-2259.
Sheng, H., Williams, C.S., Shao, J., Liang, P., DuBois, R.N., and Beauchamp, R.D. (1998). Induction of cyclooxygenase-2 by activated Ha-ras oncogene in Rat-1 fibroblasts and the role of mitogen-activated protein kinase pathway. J Biol Chem 273, 22120-22127.
Shiff, S.J., Qiao, L., Tsai, L.L., and Rigas, B. (1995). Sulindac sulfide, an aspirin-like compound, inhibits proliferation, causes cell cycle quiescence, and induces apoptosis in HT-29 colon adenocarcinoma cells. J Clin Invest 96, 491-503.
Shiotani, H., Denda, A., Yamamoto, K., Kitayama, W., Endoh, T., Sasaki, Y., Tsutsumi, N., Sugimura, M., and Konishi, Y. (2001). Increased expression of cyclooxygenase-2 protein in 4-nitroquinoline-1-oxide-induced rat tongue carcinomas and chemopreventive efficacy of a specific inhibitor, nimesulide. Cancer Res 61, 1451-1456.
Smalley, W., Ray, W.A., Daugherty, J., and Griffin, M.R. (1999). Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: a population-based study. Arch Intern Med 159, 161-166.
Solt, D.B., Calderon-Solt, L., and Odajima, T. (1985). Rapid induction of carcinomas and gamma-glutamyl transpeptidase-rich clones in N-methyl-N-benzylnitrosamine-treated hamster buccal pouch. J Natl Cancer Inst 74, 437-445.
Spanos, G.A. (1990). Influence of processing and storage on the phenolic composition of apple juice. J.Agric.food Chem. 38, 1572
Steinbach, G., Lynch, P.M., Phillips, R.K., Wallace, M.H., Hawk, E., Gordon, G.B., Wakabayashi, N., Saunders, B., Shen, Y., Fujimura, T., Su, L.K., and Levin, B. (2000). The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342, 1946-1952.
Suganuma, M., Okabe, S., Sueoka, N., Sueoka, E., Matsuyama, S., Imai, K., Nakachi, K., and Fujiki, H. (1999). Green tea and cancer chemoprevention. Mutat Res 428, 339-344.
Sumitani, K., Kamijo, R., Toyoshima, T., Nakanishi, Y., Takizawa, K., Hatori, M., and Nagumo, M. (2001). Specific inhibition of cyclooxygenase-2 results in inhibition of proliferation of oral cancer cell lines via suppression of prostaglandin E2 production. J Oral Pathol Med 30, 41-47.
Tanaka, T., Nishikawa, A., Mori, Y., Morishita, Y., and Mori, H. (1989). Inhibitory effects of non-steroidal anti-inflammatory drugs, piroxicam and indomethacin on 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male ACI/N rats. Cancer Lett 48, 177-182.
Tardieu, D., Jaeg, J.P., Deloly, A., Corpet, D.E., Cadet, J., and Petit, C.R. (2000). The COX-2 inhibitor nimesulide suppresses superoxide and 8-hydroxy-deoxyguanosine formation, and stimulates apoptosis in mucosa during early colonic inflammation in rats. Carcinogenesis 21, 973-976.
Taylor, M.T., Lawson, K.R., Ignatenko, N.A., Marek, S.E., Stringer, D.E., Skovan, B.A., and Gerner, E.W. (2000). Sulindac sulfone inhibits K-ras-dependent cyclooxygenase-2 expression in human colon cancer cells. Cancer Res 60, 6607-6610.
Thompson, H.J., Jiang, C., Lu, J., Mehta, R.G., Piazza, G.A., Paranka, N.S., Pamukcu, R., and Ahnen, D.J. (1997). Sulfone metabolite of sulindac inhibits mammary carcinogenesis. Cancer Res 57, 267-271.
Thompson, W.J., Piazza, G.A., Li, H., Liu, L., Fetter, J., Zhu, B., Sperl, G., Ahnen, D., and Pamukcu, R. (2000). Exisulind induction of apoptosis involves guanosine 3',5'-cyclic monophosphate phosphodiesterase inhibition, protein kinase G activation, and attenuated beta-catenin. Cancer Res 60, 3338-3342.
Tomozawa, S., Nagawa, H., Tsuno, N., Hatano, K., Osada, T., Kitayama, J., Sunami, E., Nita, M.E., Ishihara, S., Yano, H., Tsuruo, T., Shibata, Y., and Muto, T. (1999). Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522. Br J Cancer 81, 1274-1279.
van Lieshout, E.M., Tiemessen, D.M., Peters, W.H., and Jansen, J.B. (1997). Effects of nonsteroidal anti-inflammatory drugs on glutathione S-transferases of the rat digestive tract. Carcinogenesis 18, 485-490.
Weyant, M.J., Carothers, A.M., Dannenberg, A.J., and Bertagnolli, M.M. (2001). (+)-Catechin inhibits intestinal tumor formation and suppresses focal adhesion kinase activation in the min/+ mouse. Cancer Res 61, 118-125.
Williams, C.S., Mann, M., and DuBois, R.N. (1999). The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 18, 7908-7916.
Wilson, J.W. and Potten, C.S. (2000). The effect of exogenous prostaglandin administration on tumor size and yield in Min/+ mice. Cancer Res 60, 4645-4653.
Wolff, H., Saukkonen, K., Anttila, S., Karjalainen, A., Vainio, H., and Ristimaki, A. (1998). Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res 58, 4997-5001.
Wu-Wang, C.Y., Wang, S.L., Brigham, M., Correa, A., Slomiany, A., and Slomiany, B.L. (1993). Expression of prostaglandin E2 receptor in hamster buccal pouch: effect of benzo (a) pyrene and nicotine. Prostaglandins Leukot Essent Fatty Acids 49, 821-826.
Yang, C.S. (1980). Research on esophageal cancer in China: a review. Cancer Res 40, 2633-2644.
郭彥彬. "嚼檳榔與口腔癌基因、抑癌基因的突變和表現",國家衛生研究院,(2000):1-3.
楊奕馨. "檳榔嚼塊與口腔癌流行病學研究",國家衛生研究院,(2000):15-23.

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1. 60.鄭明娳(1987/11)〈論中國現代寓言文學〉.中外文學
2. 58.趙淑俠(2000/2)〈留學生文學的蛻變〉.文訊第172期
3. 46.喻麗清(2000/2)〈由流亡到生根,從漂泊到回歸〉.文訊第172期
4. 59.齊邦媛(1978/5)〈散文的兩個世界─由王鼎鈞的「碎琉璃」、蕭白的「響在心中的水聲」談起〉.幼獅文藝293期
5. 40.陳若曦(2000/2)〈我的海外文學生涯〉.文訊第172期
6. 37.張騰蛟(1983/8)〈不是遊記-讀王鼎鈞的《海水天涯中國人》〉.文訊第二期
7. 36.張讓(2000/2)〈鄉愁的方位〉.文訊第172期
8. 35.張大春〈寓言的箭射向光影之間─一則小說的指涉論〉.聯合文學第十三卷第七期。
9. 30.張春榮(1992/9)〈細緻與真實─王鼎鈞散文的描寫藝術〉.文訊革新第四十四期
10. 27.展甦(1983/3)〈三隻眼的旅者─讀王鼎鈞的《海水天涯中國人》〉.明道文藝
11. 12.宋瑞(1978/9)〈品鑒碎琉璃:從故事看本書的結構〉.明道文藝
12. 23.徐學(1991/7)〈世紀末與創世紀─八十年代後臺灣散文綜觀與趨勢〉.聯合文學第五卷第二期
13. 76.叢甦(2000/2)〈沙灘的腳印--「留學生文學」與流放意識〉.文訊第172期
14. 22.高天生(1978/9)〈傳統課題與文學創作:試論「碎琉璃」中的憂患意識〉.明道文藝30期
15. 15.林燿德(1995/10)〈傳統之軸與前衛之輪─半世紀的台灣散文面目〉.聯合文學132期。