Medication Advancement of Gastrointestinal Polyposis in Patients with Peutz-Jeghers Syndrome_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Shilin , GU Guoli

Department of General Surgery, General Hospital of Chinese PLA Airforce, Beijing 100042, ChinaCorresponding Author: WANG Shi-lin, E-mail: wangshilin@medmail.com.cn;

Corresponding author：

Keywords：

Peutz-Jeghers syndrome; Ｇastrointestinal tumor; Ｃyclooxygenase; Non-steroidal anti-inflammatory drug

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Objective 　To investigate the medication advancement of gastrointestinal polyposis in patients with Peutz-Jeghers syndrome (PJS).
Methods 　Literatures about the medication advancement on gastrointestinal polyposis of PJS were reviewed and analyzed. The recent development of targeting drugs, especially the data of cyclooxygenase-2 selective inhibitors and rapamycin, were emphatically summarized.
Results 　With the deep investigation of PJS and application of selective drugs, the medication of gastrointestinal polyposis in cases of PJS has got more advancement. The extensive use of synthetic cyclooxygenase-2 inhibitors and rapamycin in clinic developed a new way to treat gastrointestinal polyposis of PJS.
Conclusion 　The cyclooxygenase-2 selective inhibitors and rapamycin have the following features: noninvasive, high selectivity and good curative effects. They have splendid prospects in the clinical treatment of gastrointestinal polyposis in patients with PJS and are bring the treatment of gastrointestinal polyposis in cases of PJS into a targeting therapy phase.

Citation： WANG Shilin,GU Guoli. Medication Advancement of Gastrointestinal Polyposis in Patients with Peutz-Jeghers Syndrome. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(4): 333-335. doi: Copy

1.	董科, 李波. 黑斑息肉综合征的研究进展 [J]. 中国普外基础与临床杂志, 2005; 12(2): 195-198.
2.	蒋晓忠, 陈历恒, 严律南, 等. Peutz-Jeghers综合征及其合并癌变的临床分析 [J]. 中国普外基础与临床杂志, 2006; 13(6): 709-711.
3.	de Leng WW, Jansen M, Carvalho R, et al. Genetic defects underlying Peutz-Jeghers syndrome (PJS) and exclusion of the polarity-associated MARK/Par1 gene family as potential PJS candidates [J]. Clin Genet, 2007; 72(6): 568-573.
4.	Mehenni H, Resta N, Guanti G, et al. Molecular and clinical characteristics in 46 families affected with Peutz-Jeghers syndrome [J]. Dig Dis Sci, 2007; 52(8): 1924-1933.
5.	郑燕, 管杰, 徐忠法. COX-2 及其抑制剂与结直肠肿瘤 [J]. 肿瘤防治杂志, 2002; 9(4): 487-490.
6.	Weingarten MA, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps [J]. Cochrane Database Syst Rev, 2008; (1): CD003548.
7.	刘昌军. 选择性COX-2 抑制剂抑制结肠癌细胞生长作用的研究 [J]. 数理医药学杂志, 2005; 18(6): 599-600.
8.	方维丽, 王邦茂. 选择性COX-2 抑制剂防治结直肠腺瘤的研究进展 [J]. 天津医药, 2008; 36(4): 314-316.
9.	向阳, 孙敏, 王和勇. COX-2 及其抑制剂在肿瘤防治中的作用 [J]. 生命科学, 2008; 20(1): 81-85.
10.	Rossi DJ, Ylikorkala A, Korsisaari N, et al. Induction of cyclooxygenase-2 in a mouse model of Peutz-Jeghers polyposis [J]. Proc Natl Acad Sci USA, 2002; 99(19): 12327-12332.
11.	Wei C, Amos CI, Rashid A, et al. Correlation of staining for LKB1 and COX-2 in hamartomatous polyps and carcinomas from patients with Peutz-Jeghers syndrome [J]. J Histochem Cytochem, 2003; 51(12): 1665-1672.
12.	De Leng WW, Westerman AM, Weterman MA, et al. Cyclooxygenase 2 expression and molecular alterations in Peutz-Jeghers hamartomas and carcinomas [J]. Clin Cancer Res, 2003; 9(8): 3065-3072.
13.	Takeda H, Miyoshi H, Tamai Y, et al. Simultaneous expression of COX-2 and mPGES-1 in mouse gastrointestinal hamartomas [J]. Br J Cancer, 2004; 90(3): 701-704.
14.	Giardiello FM, Trimbath JD. Peutz-Jeghers syndrome and management recommendations [J]. Clin Gastroenterol Hepatol, 2006; 4(4): 408-415.
15.	刘伟, 安杰, 张超, 等. 塞来昔布对人结肠癌细胞生长及裸鼠肝转移瘤形成的影响 [J]. 中国普外基础与临床杂志, 2006; 13(6): 693-697.
16.	金志明, 王天翔, 尹路. Cox-2选择性抑制剂预防结直肠癌术后复发的作用 [J]. 上海交通大学学报(医学版), 2008; 28(4): 424-426.
17.	韩英, 李世荣. 环氧化酶-2(COX-2)抑制剂与肿瘤预防及治疗 [J]. 中国新药杂志, 2002; 11(6): 440-442.
18.	Keller JJ, Offerhaus GJ, Hylind LM, et al. Rectal epithelial apoptosis does not predict response to sulindac treatment or polyp development in presymptomatic familial adenomatous polyposis patients [J]. Cancer Epidemiol Biomarkers Prev, 2002; 11(7): 670-671.
19.	郭贵龙, 张筱骅, 姚榛祥. 选择性COX-2抑制剂尼美舒利对大鼠乳腺癌的影响及机理研究 [J]. 中国普外基础与临床杂志, 2005; 12(3): 219-222.
20.	邓渝林, 陶霞, 周静, 等. 第二代COX-2 抑制剂的研究进展 [J]. 解放军药学学报, 2005; 21(3): 209-213.
21.	张国华, 朱一力, 曾凡星. 5′-AMP上下游蛋白激酶与运动的关系研究进展 [J]. 成都体育学院学报, 2007; 33(3): 79-81.
22.	张俊峰, 陈规划, 陆敏强, 等. 线粒体在雷帕霉素诱导肝癌细胞Bel-7402凋亡中的作用 [J]. 中国普外基础与临床杂志, 2007; 14(3): 280-283.
23.	季曙明. 雷帕霉素免疫抑制作用机制的研究进展 [J]. 肾脏病与透析肾移植杂志, 2001; 10(5): 483-486.
24.	吴亚铭, 陈晓. 新型免疫抑制剂——西罗莫司 [J]. 天津药学, 2003; 15(2): 72-73.
25.	王志钢, 吴应积, 旭日干. mTOR信号通路与细胞生长调控 [J]. 生物物理学报, 2007; 23(5): 333-337.
26.	Podsypanina K, Lee RT, Politis C, et al. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice [J]. Proc Natl Acad Sci USA, 2001; 98(18): 10320-10325.
27.	Wei C, Amos CI, Zhang N, et al. Suppression of Peutz-Jeghers polyposis by targeting mammalian target of rapamycin signaling [J]. Clin Cancer Res, 2008; 14(4): 1167-1171.
28.	Rosner M, Hanneder M, Siegel N, et al. The mTOR pathway and its role in human genetic diseases [J]. Mutat Res, 2008; 659(3): 284-292.
29.	Inoki K, Corradetti MN, Guan KL. Dysregulation of the TSC-mTOR pathway in human disease [J]. Nat Genet, 2005; 37(1): 19-24.
30.	陆莉, 林志彬. 一种新型的免疫抑制剂——雷帕霉素 [J]. 中国药学杂志, 2001; 36(9): 643-645.
31.	Katajisto P, Vallenius T, Vaahtomeri K, et al. The LKB1 tumor suppressor kinase in human disease [J]. Biochim Biophys Acta, 2007; 1775(1): 63-75.
32.	Katajisto P, Vaahtomeri K, Ekman N, et al. LKB1 signaling in mesenchymal cells required for suppression of gastrointestinal polyposis [J]. Nat Genet, 2008; 40(4): 455-459.〖ＨＪ〗[33]Eisinger AL, Nadauld LD, Shelton DN, et al. Retinoic acid inhibits beta-catenin through suppression of Cox-2: a role for truncated adenomatous polyposis coli [J]. J Biol Chem, 2007; 282(40): 29394-29400.
33.	顾国利, 魏学明, 王石林, 等. 大肠癌E-cadherin, β-catenin, MMP-7表达及其临床意义 [J]. 世界华人消化杂志, 2007; 15(4): 375-380.

1. 董科, 李波. 黑斑息肉综合征的研究进展 [J]. 中国普外基础与临床杂志, 2005; 12(2): 195-198.
2. 蒋晓忠, 陈历恒, 严律南, 等. Peutz-Jeghers综合征及其合并癌变的临床分析 [J]. 中国普外基础与临床杂志, 2006; 13(6): 709-711.
3. de Leng WW, Jansen M, Carvalho R, et al. Genetic defects underlying Peutz-Jeghers syndrome (PJS) and exclusion of the polarity-associated MARK/Par1 gene family as potential PJS candidates [J]. Clin Genet, 2007; 72(6): 568-573.
4. Mehenni H, Resta N, Guanti G, et al. Molecular and clinical characteristics in 46 families affected with Peutz-Jeghers syndrome [J]. Dig Dis Sci, 2007; 52(8): 1924-1933.
5. 郑燕, 管杰, 徐忠法. COX-2 及其抑制剂与结直肠肿瘤 [J]. 肿瘤防治杂志, 2002; 9(4): 487-490.
6. Weingarten MA, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps [J]. Cochrane Database Syst Rev, 2008; (1): CD003548.
7. 刘昌军. 选择性COX-2 抑制剂抑制结肠癌细胞生长作用的研究 [J]. 数理医药学杂志, 2005; 18(6): 599-600.
8. 方维丽, 王邦茂. 选择性COX-2 抑制剂防治结直肠腺瘤的研究进展 [J]. 天津医药, 2008; 36(4): 314-316.
9. 向阳, 孙敏, 王和勇. COX-2 及其抑制剂在肿瘤防治中的作用 [J]. 生命科学, 2008; 20(1): 81-85.
10. Rossi DJ, Ylikorkala A, Korsisaari N, et al. Induction of cyclooxygenase-2 in a mouse model of Peutz-Jeghers polyposis [J]. Proc Natl Acad Sci USA, 2002; 99(19): 12327-12332.
11. Wei C, Amos CI, Rashid A, et al. Correlation of staining for LKB1 and COX-2 in hamartomatous polyps and carcinomas from patients with Peutz-Jeghers syndrome [J]. J Histochem Cytochem, 2003; 51(12): 1665-1672.
12. De Leng WW, Westerman AM, Weterman MA, et al. Cyclooxygenase 2 expression and molecular alterations in Peutz-Jeghers hamartomas and carcinomas [J]. Clin Cancer Res, 2003; 9(8): 3065-3072.
13. Takeda H, Miyoshi H, Tamai Y, et al. Simultaneous expression of COX-2 and mPGES-1 in mouse gastrointestinal hamartomas [J]. Br J Cancer, 2004; 90(3): 701-704.
14. Giardiello FM, Trimbath JD. Peutz-Jeghers syndrome and management recommendations [J]. Clin Gastroenterol Hepatol, 2006; 4(4): 408-415.
15. 刘伟, 安杰, 张超, 等. 塞来昔布对人结肠癌细胞生长及裸鼠肝转移瘤形成的影响 [J]. 中国普外基础与临床杂志, 2006; 13(6): 693-697.
16. 金志明, 王天翔, 尹路. Cox-2选择性抑制剂预防结直肠癌术后复发的作用 [J]. 上海交通大学学报(医学版), 2008; 28(4): 424-426.
17. 韩英, 李世荣. 环氧化酶-2(COX-2)抑制剂与肿瘤预防及治疗 [J]. 中国新药杂志, 2002; 11(6): 440-442.
18. Keller JJ, Offerhaus GJ, Hylind LM, et al. Rectal epithelial apoptosis does not predict response to sulindac treatment or polyp development in presymptomatic familial adenomatous polyposis patients [J]. Cancer Epidemiol Biomarkers Prev, 2002; 11(7): 670-671.
19. 郭贵龙, 张筱骅, 姚榛祥. 选择性COX-2抑制剂尼美舒利对大鼠乳腺癌的影响及机理研究 [J]. 中国普外基础与临床杂志, 2005; 12(3): 219-222.
20. 邓渝林, 陶霞, 周静, 等. 第二代COX-2 抑制剂的研究进展 [J]. 解放军药学学报, 2005; 21(3): 209-213.
21. 张国华, 朱一力, 曾凡星. 5′-AMP上下游蛋白激酶与运动的关系研究进展 [J]. 成都体育学院学报, 2007; 33(3): 79-81.
22. 张俊峰, 陈规划, 陆敏强, 等. 线粒体在雷帕霉素诱导肝癌细胞Bel-7402凋亡中的作用 [J]. 中国普外基础与临床杂志, 2007; 14(3): 280-283.
23. 季曙明. 雷帕霉素免疫抑制作用机制的研究进展 [J]. 肾脏病与透析肾移植杂志, 2001; 10(5): 483-486.
24. 吴亚铭, 陈晓. 新型免疫抑制剂——西罗莫司 [J]. 天津药学, 2003; 15(2): 72-73.
25. 王志钢, 吴应积, 旭日干. mTOR信号通路与细胞生长调控 [J]. 生物物理学报, 2007; 23(5): 333-337.
26. Podsypanina K, Lee RT, Politis C, et al. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice [J]. Proc Natl Acad Sci USA, 2001; 98(18): 10320-10325.
27. Wei C, Amos CI, Zhang N, et al. Suppression of Peutz-Jeghers polyposis by targeting mammalian target of rapamycin signaling [J]. Clin Cancer Res, 2008; 14(4): 1167-1171.
28. Rosner M, Hanneder M, Siegel N, et al. The mTOR pathway and its role in human genetic diseases [J]. Mutat Res, 2008; 659(3): 284-292.
29. Inoki K, Corradetti MN, Guan KL. Dysregulation of the TSC-mTOR pathway in human disease [J]. Nat Genet, 2005; 37(1): 19-24.
30. 陆莉, 林志彬. 一种新型的免疫抑制剂——雷帕霉素 [J]. 中国药学杂志, 2001; 36(9): 643-645.
31. Katajisto P, Vallenius T, Vaahtomeri K, et al. The LKB1 tumor suppressor kinase in human disease [J]. Biochim Biophys Acta, 2007; 1775(1): 63-75.
32. Katajisto P, Vaahtomeri K, Ekman N, et al. LKB1 signaling in mesenchymal cells required for suppression of gastrointestinal polyposis [J]. Nat Genet, 2008; 40(4): 455-459.〖ＨＪ〗[33]Eisinger AL, Nadauld LD, Shelton DN, et al. Retinoic acid inhibits beta-catenin through suppression of Cox-2: a role for truncated adenomatous polyposis coli [J]. J Biol Chem, 2007; 282(40): 29394-29400.
33. 顾国利, 魏学明, 王石林, 等. 大肠癌E-cadherin, β-catenin, MMP-7表达及其临床意义 [J]. 世界华人消化杂志, 2007; 15(4): 375-380.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Medication Advancement of Gastrointestinal Polyposis in Patients with Peutz-Jeghers Syndrome

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