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研究生:彭治平
研究生(外文):Peng Jyh Ping
論文名稱:第二型環氧化酶在下咽癌的表現和其專一性抑制劑對細胞凋亡與細胞週期的調控
論文名稱(外文):Expression of cyclooxygenase-2(COX-2) in hypopharyngeal cancer and modulation of apoptosis and cell cycle progression by COX-2- specific inhibitors
指導教授:蘇志英蘇志英引用關係洪文俊洪文俊引用關係
指導教授(外文):Su Chih YingHung Wen Chun
學位類別:碩士
校院名稱:長庚大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2003
畢業學年度:91
語文別:中文
論文頁數:71
中文關鍵詞:第二型環氧化酶下咽癌第二型環氧化酶專一性抑制劑
外文關鍵詞:cyclooxygenase-2hypopharyngeal cancerspecific COX-2 inhibitor
相關次數:
  • 被引用被引用:0
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  • 下載下載:16
  • 收藏至我的研究室書目清單書目收藏:1
近來研究顯示第二型環氧化酶在人類細胞的癌化過程中扮演相當重要的角色,下咽癌目前在台灣為頭頸部腫預後最差的癌症,嚼檳榔是造成下咽癌的主要因子。本研究的目的,在探討第二型環氧化酶在下咽癌腫瘤組織的表現及檳榔萃取物誘導下咽部細胞和下咽癌細胞第二型環氧化酶表現之機制,並利用專一性抑制劑來進行實驗,以評估其運用於癌症預防和治療的可能性。實驗結果得知,檳榔萃取物可促進下咽部細胞第二型環氧化酶的表現,而且第二型環氧化酶在下咽癌組織中呈現過度表現的現象。同時我們也發現在第二型環氧化酶基因轉殖的下咽部細胞或下咽癌細胞其間質金屬蛋白酶和血管內皮增生因子的表現明顯增加。我們進一步探討第二型環氧化酶專一性抑制劑對下咽癌細胞的生長、細胞凋亡以及細胞週期的影響。結果發現第二型環氧化酶專一性抑制劑(NS398),對下咽癌有細胞生長抑制作用,而且與劑量比成正相關。另外在流式細胞分析儀分析中,也發現第二型環氧化酶專一性抑制劑(NS398)可引發下咽癌細胞株(FADU) 之細胞週期停滯在G1/S期,當以不同濃度的第二型環氧化酶專一性抑制劑(NS398) 處理下咽癌細胞株(FADU) 後,調控G1/S期進行的週期蛋白的表現,不受到影響。相反的,蛋白激酶抑制蛋白p21Waf1和p27Kip1,卻明顯表現。我們也發現第二型環氧化酶專一性抑制劑可增強化學治癌藥物對下咽癌細胞的毒殺作用。此作用可能是經由加強誘導細胞凋亡所達成。結論,第二型環氧化酶與下咽癌之細胞生長及腫瘤形成有關,利用其專一性抑制劑,可用來抑制癌細胞,而且可配合抗癌化學藥物使用,以提高療效。

Recent studies demonstrate that cyclooxygenase-2(COX-2) plays a crucial role in tumorigenesis of human cancers. Hypopharyngeal cancer is one of head and neck cancers with very poor prognosis in Taiwan. Betel nut chewing is the major contributory factor of hypopharyngeal cancer. The aim of this study was investigated the expression of COX-2 in primary tumor tissues of hypopharyngeal cancer and examined the effect of betel nut ingredient on COX-2 expression in normal hypopharyngeal and cancer cells. In addition, we addressed the effect of COX-2-specific inhibitor on hypopharyngeal cancer cells to evaluate whether these inhibitors might be useful for the prevention or treatment of this cancer. Betel nut ingredients promoted COX-2 expression in normal hypophaygeal and hypopharyngeal cancer cells. Our results also showed that COX-2 was overexpressed in hypophaygeal tumor tissues. Transfection of COX-2 expression vector in hypopharyngeal cells or cancer cells stimulated the expression of matrix metalloproteinases and vascular endothelial growth factor. We next tested the effect of COX-2- specific inhibitor NS398 on the proliferation, apoptosis, and cell cycle progression of hypopharyngeal cancer cells. Results showed that specific COX-2 inhibitor (NS398) inhibited growth of cancer cell in a dose-dependent manner and arrested hypopharyngeal cancer cells in G1/S phase. Immunoblotting analysis indicated that expression of G1 cyclins was not change by NS398. Conversely, NS398 obviously increased expression of cyclin-dependent kinases inhibitors p21Waf1 and p27Kip1. Pretreatment of NS398 potently enhanced the cytocidal activity of chemotherapeutic drugs. This effect is possibly mediated via enhancement of apoptosis. Taken together, COX-2 is involved in tumorigenesis of hypophaygeal cancer and COX-2 inhibitors exert anti-proliferative effect on hypopharyngeal cancer cells and may be used in combination with chemotherapeutic drugs for the treatment of hypopharyngeal carcinoma.

指導教授推薦書…………………………………………………… i
口試委員審定書…………………………………………………ii
授權書……………………………………………………………iii
內容目錄…………………………………………………………vi
圖目錄……………………………………………………………ix
表目錄……………………………………………………………xii
中文摘要…………………………………………………………xiii
英文摘要…………………………………………………………xv
誌謝………………………………………………………………xvii
第一章、前言…………………………………………………1
1.1 下咽部解剖及下咽癌……………………………………1
1.2 下咽部癌化因子…………………………………………3
1.3第二型環氧化酶和下咽癌的關係………………………4
1.4第二型環氧化酶抑制劑與下咽癌抑癌的相關性……………6
1.5第二型環氧化酶專一性抑制劑抑制下咽癌細胞生長分析
細胞週期調節性蛋白的相關性………………………………8
第二章、論文研究目的…………………………………………11
第三章、實驗材料和方法…………………………………13
3.1 實驗材料………………………………………………13
3.2 實驗方法………………………………………………18
第四章、結果………………………………………………27
4.1. 下咽癌組織與第二型環氧化酶的表現…………………27
4.2. 檳榔萃取物刺激正常下咽部細胞與第二型
環氧化酶的蛋白質的表現……………………………28
4.3. 第二型環氧化酶對下咽部正常細胞及下咽癌細胞的
調控下,對第二型間質金屬蛋白酶、第九型間質金
屬蛋白酶和血管內皮增生因子的影響…………………28
4.4. 第二型環氧化酶專一性抑制劑( NS398 )對下咽癌
細胞生長的影響………………………………………29
4.5. 第二型環氧化酶專一性抑制劑( NS398 )或合併抗
癌藥物對下咽癌細胞來進行加成毒殺作用…………29
4.6. 利用細胞流體儀分析,第二型環氧化酶專一性抑制
劑( NS398 ) 引發下咽癌細胞之細胞週期停滯在
Go /G1期…… 30
4.7. 第二型環氧化酶專一性抑制劑( NS398 )或合併抗癌
藥物對下咽癌細胞透過細胞凋亡途徑來進行毒殺作
用…………… 30
4.8. 第二型環氧化酶專一性抑制劑( NS398 ) 抑制下咽癌
細胞生長引發細胞週期停滯在G1/S期分析細胞週期調節
性蛋白的影響…………………………………………………32
第五章、討論………………………………………………33
第六章、結論建議與未來研究……………………………41
參考文獻……………………………………………………61

1. Amarante-Medndes, G.P., Naekyung Kim, C., Liu, L., Huang,
Y., Perkins, C.L., Greens, D.R., Bhala, K., 1998, “Ber-Abl
exerts its antiapoptotic effect against diverse apoptotic
stimuli through blockage of mitochondrial release of
cytochrome C and activation of caspase-3,” Blood,
Vol. 91, pp. 1700-1705.
2. Anttonen, A., Kajanti, M., Heikkila, P., Jalkanen, M.,
Joensuu, H., 1999, “Syndecan-1 expression has prognostic
significance in head and neck carcinoma,” Br. J. Cancer,
Vol.79, pp.558-64.
3. Boise, L.H., Gonzalez-Garcia, H., Postema, C.E., Ding, L.,
Dindsten, T., Turka, C.A., Maox, N.G., Thompson, C.B., 1993,
“Bcl-x a dominant regulator of apoptotic cell death,” Cell,
Vol. 74, pp. 597-608.
4. Boucher, B.J., Mannan, N., 2002, “ Metabolic effects of the
consumption of Areca catechu,” [Review] [60 refs] Addict.
Biol., Vol. 7, pp. 103-110.
5. Charous, S.J., Stricklin, G.P., Nanney, L.B., Netterville,
J.L., Burkey, B.B., 1997, “ Expression of matrix
metalloproteinases and tissue inhibitor of
metalloproteinases in head and neck squamous cell carcinoma.
Ann. Otol. Rhinol. Laryngol., Vol.80, pp.1412-1419.
6. Chen, W.S., Wei, S.J., Liu, J.M., Hsiao, M., Lin, J.K.,
Yang, W.K., 2001, “ Tumor invasiveness and liver metastasis
of colon cancer cells correlated with cyclooxygenase-2 (COX-
2) expression and inhibited by a COX-2 selective inhibitor,
Etodolac,” Int. J. Cancer., Vol. 91,
pp. 894-899.
7. Cianchi, F., Cortesini, C., Bechi, P., Fantappie, O.,
Messerini, L., Vannacci, A., Sardi, I., Baroni, G., Boddi,
V., Mazzanti, R., Masini, E., 2001, “Up-regulation of
cyclooxygenase 2 gene expression correlates with tumor
angiogenesis in human colorectal cancer,” Gastroenterol.,
Vol. 121, pp. 1339-1347
8. Corcoran, M.L., Stetler-Stevenson, W.G., Dewitt, D.L., Watl,
L.M., 1994, “Effect of cholera toxin and pertussis toxin on
prostaglandin H synthase-2, prostahgandin E2, and matrix
metalloproteinase production by human monocytes,” Arch
Biochem. Biophys., Vol. 30, pp. 481-488.
9. Daimon, H., Sawada, S., Asakura, S., Sagami, F., 1998, “In
vivo genotoxicity and DNA adduct levels in the liver of rats
treated with safrole,” Carcinogenesis, Vol. 19, pp.141-146.
10. Das, C.M., Schantz, S.P., Shillitoe, E.J., 1993, “Antibody
to a mutagenic peptide of herpes simplex virus in young
adult patients with cancer of the head and neck” Oral Surg.
Oral Med. Oral Pathol. Oral Radiol. Endod., Vol. 75, pp. 610-
614.
11. Dubois, R.N., Abramson, S.B., Crofford, L., Gupta, R.A.,
Simon, L.S., Van De Putte, L.B., Lipsky, P.E., 1998, “
Cyclooxygenase in biology and disease,” [Review]
[117 refs] FASEB. J., Vol. 12, pp. 1063-73.
12. el-Deiry, W.S., Tokino, T., Velculescu, V.E., Levy, D.B.,
Parsons, R., Trent, J.M., Lin, D., Mercer, W.E., Kinzier,
K.W., Vogelstein, B., 1993, “WAF1, a potential mediator of
p53 tumor suppression,” Cell, Vol. 75, pp. 817-822.
13. Gilhooly, E.M., Rose, D.P., 1999, “The association between
a muted ras gene and cyclooxygenase-2 expression in human
breast cancer cell line,” Int. J. Oncol., Vol. 15, pp. 267-
270.
14. Gleich, L.L., Salamone, F.N., 2002, “Molecular genetics of
head and neck cancer,” [Review] [107 refs] Cancer Control,
Vol. 9, pp. 369-378.
15. Grosch, S., Tegeder, I., Niederberger, E., Brautigam, L.,
Geisslinger, G., 2001, “COX-2 independent induction of
cell cycle arrest and apoptosis in colon cancer cells by
the selective COX-2 inhibitor celecoxib,” FASEB J., Vol.
15, pp. 27421-27424.
16. Gupta, S., Srivastava. M., Ahmad, N., Bostwick, D.G.,
Mukhtar, H.,2000, “Over-expression of cyclooxygenase-2 in
human prostate adenocarcinoma,” Prostate, Vol.42, pp. 73-
78.
17. Hamelin, R., Laurent-Pug, P., Oschwang, S., Jego, N.,
Asselain, B., Rvikos, Y., Girodet, J., Salmon, R.J.,
Thomas, G., 1994, “Association of p53 mutations with short
survival in colorectal cancer,” Gastroenterol., Vol. 106,
pp. 42-46.
18. Ho, C.M., Lam, K.H., Wei, W.I., Yuen, P.W., Lam, C.K.,
1993, “Squamous cell carcinoma of the hypopharynx -
analysis of treatment results,” Head Neck, Vol. 15, pp.
405-412.
19. Ho, P.S., Ko, Y.C., Yang, Y.H., Shieh, T.Y., Tsai, C.C.,
2002, “The incidence of oropharyngeal cancer in Taiwan:
an endemic betel quid chewing area,” J. Oral. Pathol.
Med., Vol. 31, pp. 213-219.
20. Hong, S.D., Hong, S.P., Lee, J.I., Lim, C.Y., 2000,
“Expression of matrix metalloproteinase-2 and -9 in oral
squamous cell carcinomas with regard to the metastatic
potential,” Oral Oncol.,Vol. 36, pp.207-213.
21. Hull, M., Lieb, K., Fiebich, BL., 2002, “Pathways of
inflammatory action in Alzheimer’s disease : potential
targets for disease modifying drugs,” Curr. Med. Chem.,
Vol.9, pp. 83-88.
22. Johnson, J.T., Bacon, G.W., Myers, E.N., Wagner, R.L.,
1994, “ Medial vs lateral wall pyriform sinus carcinoma:
implications for management of regional lymphatics, “ Head
Neck, Vol. 16, pp. 401-405.
23. Jeng, J.H., Chang, M.C., Hahn, L.J., 2001, “ Role of areca
nut in betel quid-associated chemical carcinogenesis:
current awareness and future perspectives,”[Review] [145
refs] Oral Oncol., Vol. 37, pp. 477-492.
24. Jones, M.K., Wang, H., Peskar, B.M., Levin, E., Itani,
.M., Sarfeh, I.J., Tarnawski, A.S., 1999, “Inhibition of
angiogenesis by nonsteroidal anti-inflammary drugs :
Insight into mechanisms and implications for cancer growth
and ulcer healing,” Nat. Med., Vol. 5, pp. 1418-1423.
25. Kerr, J.F., Wyllie, A.H., Currie, A.R., 1972, “ Apoptosis:
a basic biological phenomenon with wide-ranging
implications in tissue kinetics,” [Review] [68 refs]
Br. J. Cancer, Vol.26, pp. 239-257.
26. Keyomarsi, K., Tucker, S.L., Buchholz, T.A., Callister, M.,
Ding, Y., Hortobagyi, G.N., Bedrosian, I., Knickerbocker,
C., Toyofuku, W., Lowe, M., Herliczek. T.W., Bacus, S.S.,
2002, “Cyclin E and survival in patients with breast
cancer. N. Engl. J. Med., Vol. 347, pp. 1566-1575.
27. Ko, Y.C., Chiang, T.A., Chang, S.J., Hsieh, S.F., 1992,
“Prevalence of betel guit chewing habit in Taiwan and
related sociodemographic factors,” J. Oral. Pathol.
Med., Vol. 21, pp. 261-264.
28. Koga, H. Sakisaka, S. Ohishi, M., 1999 “Expression of
cyclooxygenase-2 in human hepatocellular carcinoma:
relevance to tumor dedifferentiation,” Hepatology, Vol.
29, pp. 688-696.
29. Ko, Y.C., Hung, Y.L., Lee, C.H., Chen, M.J., Lin, L.M.,
Tsai, C.C., 1995, “Betel quid chewing, cigarette smoking
and alochol consumption related to oral cancer in Taiwan,”
J. Oral. Pathol. Med., Vol.24, pp. 450-453.
30. Kok, S.H., Lee. J.J., Hsu, H.C., Chiang, C.P., Kuo, Y.S.,
Kuo, M.Y., 2002, “Mutations of the adenomatous polyposis
coli gene in areca quid and tobacco-associated oral
squamous cell carcinomas in Taiwan. J. Oral. Pathol. Med.,
Vol. 31, pp. 395-401.
31. Kondo, M., Yamamoto, H., Nagano, H., Okami, J., Ito, Y.,
Shimizu, J., Eguchi, H., Miyamoto, A., Dono, K., Umeshita,
K., Matsuura, N., Wakasa, K., Nakamori, S., Sakon, M.,
Monden, M., 1999, “Increased expression of COX-2 in
nontumor liver tissue Is associated with shorter disease-
free survival in patients with hepatocellular carcinoma,”
Clin. Cancer Res., Vol. 5, pp. 4005-4012.
32. Kudo, Y., Takata, T., Ogawa, I., Kaneda, T., Sato, S.,
Takekoshi, T., Zhao, M., Miyauchi, M., Nikai, H., 2000,
“p27Kip1 accumulation by inhibition of proteasome function
induces apoptosis in oral squamous cell carcinoma cells,”
Clin. Cancer Res., Vol. 6, pp. 916.
33. Kusukawa, J., Sasaguri, Y., Shima, I., Kameyama, T.,
Morimatsu, M.,1993, “Expression of matrix
metalloproteinase-2 related to lymph node metastasis of
oralsquamous cell carcinoma. A clinicopathologic study,”
Am. J. Clin. Pathol., Vol. 99, pp. 18-23.
34. Langenbach, R., Loftin, C.D., Lee, C., Tiano, H., 1999, “
Cyclooxygenase-deficient mice. A summary of their
characteristics and susceptibilities to inflammation and
carcinogensis,” Ann. N. Y. Acad. Sci., Vol. 889, pp. 52-61.
35. Lin, D.T., Subbaramaiah, K., shah, J.P., Dannenberg, Boyle,
J.O., 2002, “Cyc1ooxygenases-2 : a novel molecular target
or the prevention and treatment of head and neck cancer,”
[Review] [97 refs] Head Neck, Vol. 24, pp. 792-799.
36. Leahy, K.M., Ornberg, R.L., Wang, Y., Zweifel, B.S., Koki,
A.T., Masferrer, J.L., 2002, “ Cyclooxygenase-2 inhibition
by celecoxib reduced proliferation in induces apoptosis in
angiogenic endothelial cells in vivo,” Cancer Res., Vol.
62 pp. 625-631.
37. Lowe, S.W., Ruley, H.E., Jacks, T., Housman, D.E., 1993,
“P53-dependent apoptosis modulates the cytotoxicity of
anticancer agents,” Cell, Vol. 74, pp. 957-967.
38. Marks, S.C., Lolachi, C.M., Shamsa, F., Robinson, K., Aref,
A., Jacobs, J.R., 1996, “Outcome of pyriform sinus cancer:
a retrospective institutional review,” Laryngoscope., Vol.
106, pp. 27-31.
39. Masferrer, J.L., Leahy, K.M., Koki, A.T., Zweifel, B.S.,
Settle, S.L., Woerner, B.M., Edwards, D.A., Flickinger,
A.G., Moore, R.J., Seibert, K., 2000, “ Antiangiogenic and
antitumor activities of cyclooxygenase-2 inhibitors,”
Cancer Res., Vol. 60, pp. 1306-1311.
40. Mitchell, J.A., Warner, T.D., 1999, “Cyclooxygenase-2 :
pharmacology, physiology, biochemistry and relevance to
NSAID therapy,” Br. J. Pharmacol., Vol. 128, pp. 121-132.
41. Oh, S.J., Jeltsch, M.M., Birkenhager, R,, McCarthy, J.E.,
Weich, H.A., Christ, B., Alitalo, K., Wilting, J., 1997,
“VEGF and VEGF-C: specific induction of angiogenesis and
lymphangiogenesis in the differentiated avian
chorioallantoic membrane,” Deve. Biol., Vol.188, pp. 96-
109.
42. Ota, S., Bamba, H., Kato, A., Kawamoto, C., Yoshida, Y.,
Fujiwara, K., 2002, “COX-2, prostanoids and colon
cancer,” [Review] [44 refs] Aliment. Pharmacol. Ther.,
Vol. 16, pp.102-106.
43. Petrocelli, T., Poon, R., Drucker, D.J., Slingerland, J.M.,
Rosen, C.F., 1996, “UVB radiation induces p21 Cip1/waf1
and mediates G1 and S phase checkpoints,” Oncogene, Vol.
12, pp. 1387-1396.
44. Paccani, S.R., Boncristiano, M., Ulivieri, C., D’Elions,
M.M., Prete, G.D., Baldari, C., 2002, “ Nonsteroidal anti-
inflammatory drugs suppress T-cell activation by inhibiting
p38 MAPK induction,” J. Biol. Chem., Vol. 277 pp. 1509-
1513.
45. Randerath, K., Haglund, R.E., Phillips, D.H., 1984 “32p-
post-labelling analysis of DNA adducts formed in the livers
of animals treated with safrole, estragole and other
naturally-occurring alkenglbenzenes I adult female CD-1
mice,” Carcinogenesis, Vol. 5, pp. 1613-1622.
46. Ranelletti, F.O., Almadori, G., Rocca, B., 2001
“Prognostic significance of cyclooxygenase-2 in laryngeal
squamous cell carcinoma,” Int. J. Cancer, Vol. 95, pp.
343-349.
47. Rice, P.L., Goldberg, R.J., Ray, E.C., Driggers, L.J.,
Ahnen, D.J., 2001, “ Inhibtion of extracellular signal-
regulated kinase 1/2 phosphorylation and induction of
apoptosis by sulindac metabolites,” Cancer Res., Vol. 61,
pp. 1541-1547.
48. Riley, S.C., Webb, C.J., Leask, R., McCaig, F.M., Howe,
D.C., 2000, “Involvement of matrix metalloproteinases 2
and 9, tissue inhibitor of metalloproteinases and apoptosis
in tissue remodelling in the sheep placenta,” J. Reprod.
Fertil., Vol.118, pp. 19-27.
49. Serrano, M., Hannon, G.J., Beach, D., 1993, “a new
regwlatory motif in cell-cycle contro l causing specific
inhibition of cychn D/CDK4,” Nature Vol. 366, pp. 704-707.
50. Shiff, S.J., Rigas, B., 1997, “ Nonsteroid anti-
inflammatory drogs and colorectal cancer : envoling
concepts of their chemopreventive actions,”
Gastroenterol., Vol. 113, pp. 1992-1998.
51. Simon, C., Hicks, M.J., Nemechek, A.J., Mehta, R.,
O'Malley, B.W., Goepfert, H., Flaitz, C.M., Boyd, D., 1999,
“ PD 098059, an inhibitor of ERK1 activation, attenuates
the in vivo invasiveness of head and neck squamous cell
carcinoma,” Br. J. Cancer, Vol. 80, pp. 1412-1419.
52. Su, C.Y., Hwang, C.F., 1993, “ Near-total
laryngopharyngectomy with pectoralis major myocutaneous
flap in advanced pyriform carcinoma. J. Laryngol. Otol.,
Vol. 107, pp. 817-820.
53. Rozic, J.G., Chakrabory, C., Lala, P.K., 2001, “
Cyclooxygenase inhibitors retard murine mammary tumor
progression by reducing tumor cell migration, invasiveness
and angiogenesis,” Int. J. Cancer, Vol. 93, pp. 497-506.
54. Sawaoka, H., Tsuji, S.,, Tsujii, M., Gunawan, E.S., Sasaki,
Y., Kawano, S., Hori, M., 1999, “Cyclooxygenase inhibitors
suppress angiogenesis and reduce tumor growth in vivo,”
Lab. Invest., Vol. 79, pp. 1469-1477.
55. Sherr, C.J., 1993, “Mammalian G1 cyclins,” Cell, Vol. 73
pp. 1059-1065.
56. Shiff, S.J., Rigas, B., 1997, “ Nonsteroid anti-
inflammatory drogs and colorectal cancer : envoling concepts
of their chemopreventive actions,” Gastroenterol.,” Vol.
113, pp. 1992-1998.
57. Simon, L.S., 1999, “Role and regulation of cyclooxygenase-
2 during inflammation,” Am. J. Med., Vol. 106, pp. 37-42.
58. Takahashi, Y., Kawahara, F., Noguchi, M., Miwa, K., Sato,
., Seiki, M., Inoue, H., Tanabe, T., Yoshimoto, T., 1999,
“ Activation of matrix metalloproteinase-2 in human breast
cancer cells overexpressing cyclooxygenase-1 or —2,”
FEBS. Lett., Vol. 460, pp. 145-148.
59. Thun, M.J., Namboodiri, M.M., Heath, C.W., 1991, “Aspirin
use and reduced risk of fetal colon cancer,” N. Engl.
J.Med., Vol. 325, pp. 1593-1596.
60. Thyss, A., Schneider, M., Santini, J., Caldani, C.,
Vallicioni, J., Chauvel, P., Demard, F., 1986, “Induction
chemotherapy with cis-platinum and 5-fluorouracil for
squamous cell carcinoma of the head and neck,” Br. J.
Cancer, Vol. 54, pp. 755-60.
61. Tsujii, M., Kawano, S., DuBois, R.N., 1997,
“Cyclooxygenase-2 expression in human colon cancer cells
increases metastatic potential,” Proc. Natl. Acad. Sci.,
Vol. 94, pp. 3336-3340.
62. van den Heuvel, S., Harlow, E., 1993, “ Distinct roles for
cyclin-dependent kinases in cell cycle control,” Science,
Vol. 262,pp. 2051-2054.
63. Vainio, H., Morgan, G., 1998, “Cyclooxygenase-2 and breast
cancer prevention. Non- steriodal anti-inflammatory agents
are worth testing in breast cancer,” BMJ., Vol. 317, pp.
828.
64. Weitzman, S.A., Gordon, L.I., 1990, “Inflammation and
cancer: role of phagocyte-generated oxidants in
carcinogenesis,” Blood, Vol. 76, pp. 655-663.
65. Willoughby, D.A., Moore, A.R., Colville-Nash, P.R., 2000,
“COX-1, COX-2, and COX-3 and the future treatment of
chronic inflammatory disease,” Lancet, Vol. 355, pp. 646-
648.
66. Yang, C.Y., Meng, C.L., 1994, “Regulation of PG synthase
by EGF and PDGF in human oral, breast, stomach, and
fibrosarcoma cancer cell line,” J. Dent. Res., Vol. 73,
pp. 1407-1415.
67. Yatabe, Y., Masuda, A., Koshikawa, T., Nakamura, S.,
Kuroishi, T., Osada, H., Taahashi, T., Mitsudomi, T.,
Takahashi, T., 1998, “p27KIP1 in human lung cancers:
differential changes in small cell and non-small cell
carcinomas,” Cancer Res., Vol. 58, pp. 1042-1047.
68. Yoshizaki, T., Maruyama, Y., Sato, H., Furukawa, M., 2001
“Expression of tissue inhibitor of matrix metalloproteinase-
2 correlates with activation of matrix metalloproteinase-2
and predicts poor prognosis in tongue squamous cell
carcinoma,” Int. J. Cancer, Vol. 95 pp. 44-50
69. Xiong, Y., Hannon, G.J., Zhang, H., Casso, D., Kobayashi,
K., Beach, D.,1993, “p21 is a universal inhibitor of
cyclin kinases,” Nature, Vol. 366, pp. 701-702.
70. Zhang, Y., Dewitt, D.L., McNeely, T.B., Wahl, S.M., Wahl,
L.M., 1997, “ Secretory leukocyte protease inhibitor
suppresses the production of monocyte prostaglandin H
synthase-2, prostaglandin E2, and matrix metalloproteinase.
J. Clin. Invest.,” Vol. 99, pp. 894-900.

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