• 1.山東省即墨市人民醫(yī)院胃腸外科(即墨266200);;
  • 2.山東省即墨市人民醫(yī)院病理科(即墨266200）;

目的 介紹近年來(lái)抑癌基因p53和癌基因c-erbB-2與胃癌關(guān)系的研究進(jìn)展。
方法 收集近年來(lái)國(guó)內(nèi)、外關(guān)于胃癌中p53和c-erbB-2的相關(guān)文獻(xiàn)并進(jìn)行綜述。
結(jié)果 p53基因突變和c-erbB-2的過表達(dá)是胃癌發(fā)生中的常見事件。p53突變與胃癌的發(fā)生部位及其侵襲性生物學(xué)行為有關(guān); c-erbB-2的過表達(dá)可作為判斷胃癌預(yù)后的獨(dú)立參數(shù)。針對(duì)p53及c-erbB-2的基因靶向治療藥物也在不斷研究中。結(jié)論 深入研究p53與c-erbB-2基因在胃癌發(fā)生、發(fā)展中的作用，將有助于清楚地認(rèn)識(shí)胃癌的生物學(xué)行為，并為胃癌的基因治療提供理論依據(jù)。

引用本文： 王宏波,紀(jì)常生,張軍. p53和c-erbB-2與胃癌關(guān)系的研究進(jìn)展. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010, 17(8): 880-884. doi: 復(fù)制

1. 陳志新, 張波. 胃癌綜合治療現(xiàn)狀及展望 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2008; 15(1): 7173.
2. Smith MG, Hold GL, Tahara E, et al. Cellular and molecular aspects of gastric cancer [J]. World J Gastroenterol, 2006; 12(19): 29792990.
3. Cunningham SC, Kamangar F, Kim MP, et al. Claudin4, mitogenactivated protein kinase kinase 4, and stratifin are markers of gastric adenocarcinoma precursor lesions [J]. Cancer Epidemiol Biomarkers Prev, 2006; 15(2): 281287.
4. Meireles SI, Cristo EB, Carvalho AF, et al. Molecular classifiers for gastric cancer and nonmalignant diseases of the gastric mucosa [J]. Cancer Res, 2004; 64(4): 12551265.
5. Sun Y, Li JY, He JS, et al. Tissue microarray analysis of multiple gene expression in intestinal metaplasia, dysplasia and carcinoma of the stomach [J]. Histopathology, 2005; 46(5): 505514.
6. Correa P. Human gastric carcinogenesis: a multistep and multifactorial processFirst American Cancer Society Award Lecture on Cancer Epidemiology and Prevention [J]. Cancer Res, 1992; 52(24): 67356740.
7. Busuttil RA, Boussioutas A. Intestinal metaplasia: a premalignant lesion involved in gastric carcinogenesis [J]. J Gastroenterol Hepatol, 2009; 24(2):193201.
8. Tamura G. Alterations of tumor suppressor and tumorrelated genes in the development and progression of gastric cancer [J]. World J Gastroenterol, 2006; 12(2): 192198.
9. Laptenko O, Prives C. Transcriptional regulation by p53: one protein, many possibilities [J]. Cell Death differ, 2006; 13(6): 951961.
10. Egashira A, Morita M, Kakeji Y, et al. p53 gene mutations in esophageal squamous cell carcinoma and their relevance to etiology and pathogenesis: results in Japan and comparisons with other countries [J]. Cancer Sci, 2007; 98(8): 11521156.
11. Kim E, Giese A, Deppert W. Wildtype p53 in cancer cells: when a guardian turns into a blackguard [J]. Biochem Pharmacol, 2009; 77(1):1120.
12. Han JA, Kim J, Ongusaha PP, et al. p53mediated induction of Cox2 counteracts p53 or genotoxic stressinduced apoptosis [J]. EMBO J, 2002; 21(21): 56355644.
13. Olivier M, Eeles R, Hollstein M, et al. The IARC TP53 database： New online mutation analysis and recommendations to users [J]. Hum Mutat, 2002; 19(6): 607614.
14. PintodeSousa J, Silva F, David L, et al. Clinicopathological significance and survival influence of p53 protein expression in gastric carcinoma [J]. Histopathology, 2004; 44(4): 323331.
15. Tamura G, Sato K, Akiyama S, et al. Molecular characterization of undifferentiatedtype gastric carcinoma [J]. Lab Invest, 2001; 81(4): 593598.
16. Shiao YH, Palli D, Buzard GS, et al. Implications of p53 mutation spectrum for cancer etiology in gastric cancers of various histologic types from a highrisk area of central Italy [J]. Carcinogenesis, 1998; 19 (12): 21452149.
17. Morgan C, Jenkins GJ, Ashton T, et al. Detection of p53 mutations in precancerous gastric tissue [J]. Br J Cancer, 2003; 89(7): 13141319.
18. Taguchi A, Ohmiya N, Itoh A, et al. Severity of atrophic gastritis related to antiparietal cell antibody and gastric carcinogenesis, including p53 mutations [J]. J Gastroenterol Hepatol, 2006; 21(3): 545551.
19. Azarhoush R, Keshtkar AA, Amiriani T, et al. Relationship between p53 expression and gastric cancers in cardia and antrum [J]. Arch Iran Med, 2008; 11(5): 502506.
20. Tajima Y, Yamazaki K, Makino R, et al. Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach [J]. Br J Cancer, 2007; 96(4): 631638.
21. Nayak SK, Panesar PS, Kumar H. p53Induced apoptosis and inhibitors of p53 [J]. Curr Med Chem, 2009; 16(21): 26272640.
22. Ohnishi T, Takahashi A, Mori E, et al. p53 Targeting can enhance cancer therapy via radiation, heat and anticancer agents [J]. Anticancer Agents Med Chem, 2008; 8(5): 564570.
23. Yano T, Ochiai A, Doi T, et al. Expression of HER2 in gastric cancer: Comparison between protein expression and gene amplification using a new commercial kit [J]. J Clin Oncol, 2004; 22(14S): 4053.
24. Rastelli F, Crispino S. Factors predictive of response to hormone therapy in breast cancer [J]. Tumori, 2008; 94(3): 370383.
25. Schuell B, Gruenberger T, Scheithauer W, et al. HER2/neu protein expression in colorectal cancer [J]. BMC Cancer, 2006; 6: 123127.
26. Eltze E, Wülfing C, Von Struensee D, et al. Cox2 and Her2/neu coexpression in invasive bladder cancer [J]. Int J Oncol, 2005; 26(6):15251531.
27. Sakai K, Mori S, Kawamoto T, et al. Expression of epidermal growth factor receptors on normal human gastric epithelia and gastric carcinomas [J]. J Natl Cancer Inst, 1986; 77(5): 10471052.
28. Park DI, Yun JW, Park JH, et al. HER2/neu amplification is an independent prognostic factor in gastric cancer [J]. Dig Dis Sci, 2006; 51(8): 13711379.
29. Gravalos C, Mrquez A, GarcíaCarbonero R, et al. Correlation between Her2/neu overexpression/amplification and clinicopathological parameters in advanced gastric cancer (AGC) patients (pts): A prospective study [C]. 2007 Gastrointestinal Cancers Symposium， 2007； Abstract No: 89.
30. Lordick F, Bang YJ, Kang YK, et al. HER2positive advanced gastric cancer: similar HER2positivity levels to breast cancer [J]. Eur J Cancer, 2007; 5(4): 271277.
31. Tanner M, Hollmén M, Junttila TT, et al. Amplification of HER2 in gastric carcinoma: association with Topoisomerase II gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab [J]. Ann Oncol, 2005; 16(2): 273278.
32. Nicholas G, Cripps C, Au HP, et al. Early results of a trial of trastuzumab, cisplatin and docetaxel for the treatment of metastatic gastric cancer overexpressing HER2 [J]. ESMO, 2006; 17 (Suppl 9): 316.
33. 汪劭婷, 朱朝暉, 李小毅. 胃癌新輔助化療療效臨床評(píng)價(jià)方法及進(jìn)展 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010; 17(2): 200204.
34. Sastre J, GarciaSaenz JA, DiazRubio E. Chemotherapy for gastric cancer [J]. World J Gastroenterol, 2006; 12(2): 204213.
35. Rech J, Arnold D, Folprecht G, et al. A pilot study of trastuzumab monotherapy in patients who progressed while on chemotherapy for metastatic or locally advanced HER2 positive gastric cancer [J]. ESMO, 2006; 17 (Suppl 9): 314.
36. Kim SY, Kim HP, Kim YJ, et al. Trastuzumab inhibits the growth of human gastric cancer cell lines with HER2 amplification synergistically with cisplatin [J]. Int J Oncol, 2008; 32(1): 8995.
37. MezaJunco J, Au HJ, Sawyer MB. Trastuzumab for gastric cancer [J]. Expert Opin Biol Ther, 2009; 9(12):15431551.
38. Kang Y, Bang Y, Lordick F, et al. Incidence of gastric and gastroesophageal cancer in the ToGA trial: Correlation with HER2 positivity [C]. 2008 Gastrointestinal Cancers Symposium, 2008: 75 (Abstr 11).
39. FujimotoOuchi K, Sekiguchi F, Yasuno H, et al. Antitumor activity of trastuzumab in combination with chemotherapy in human gastric cancer xenograft models [J]. Cancer Chemother Pharmacol, 2007; 59(6): 795805.
40. Van Cutsem E, Kang Y, Chung H, et al. Efficacy results from the ToGA trial: A phase Ⅲ study of trastuzumab added to standard chemotherapy (CT) in firstline human epidermal growth factor receptor 2 (HER2)positive advanced gastric cancer (GC) [J]. J Clin Oncol, 2009; 27(18S): LBA4509.
  1. 1. 陳志新, 張波. 胃癌綜合治療現(xiàn)狀及展望 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2008; 15(1): 7173.
  2. 2. Smith MG, Hold GL, Tahara E, et al. Cellular and molecular aspects of gastric cancer [J]. World J Gastroenterol, 2006; 12(19): 29792990.
  3. 3. Cunningham SC, Kamangar F, Kim MP, et al. Claudin4, mitogenactivated protein kinase kinase 4, and stratifin are markers of gastric adenocarcinoma precursor lesions [J]. Cancer Epidemiol Biomarkers Prev, 2006; 15(2): 281287.
  4. 4. Meireles SI, Cristo EB, Carvalho AF, et al. Molecular classifiers for gastric cancer and nonmalignant diseases of the gastric mucosa [J]. Cancer Res, 2004; 64(4): 12551265.
  5. 5. Sun Y, Li JY, He JS, et al. Tissue microarray analysis of multiple gene expression in intestinal metaplasia, dysplasia and carcinoma of the stomach [J]. Histopathology, 2005; 46(5): 505514.
  6. 6. Correa P. Human gastric carcinogenesis: a multistep and multifactorial processFirst American Cancer Society Award Lecture on Cancer Epidemiology and Prevention [J]. Cancer Res, 1992; 52(24): 67356740.
  7. 7. Busuttil RA, Boussioutas A. Intestinal metaplasia: a premalignant lesion involved in gastric carcinogenesis [J]. J Gastroenterol Hepatol, 2009; 24(2):193201.
  8. 8. Tamura G. Alterations of tumor suppressor and tumorrelated genes in the development and progression of gastric cancer [J]. World J Gastroenterol, 2006; 12(2): 192198.
  9. 9. Laptenko O, Prives C. Transcriptional regulation by p53: one protein, many possibilities [J]. Cell Death differ, 2006; 13(6): 951961.
  10. 10. Egashira A, Morita M, Kakeji Y, et al. p53 gene mutations in esophageal squamous cell carcinoma and their relevance to etiology and pathogenesis: results in Japan and comparisons with other countries [J]. Cancer Sci, 2007; 98(8): 11521156.
  11. 11. Kim E, Giese A, Deppert W. Wildtype p53 in cancer cells: when a guardian turns into a blackguard [J]. Biochem Pharmacol, 2009; 77(1):1120.
  12. 12. Han JA, Kim J, Ongusaha PP, et al. p53mediated induction of Cox2 counteracts p53 or genotoxic stressinduced apoptosis [J]. EMBO J, 2002; 21(21): 56355644.
  13. 13. Olivier M, Eeles R, Hollstein M, et al. The IARC TP53 database： New online mutation analysis and recommendations to users [J]. Hum Mutat, 2002; 19(6): 607614.
  14. 14. PintodeSousa J, Silva F, David L, et al. Clinicopathological significance and survival influence of p53 protein expression in gastric carcinoma [J]. Histopathology, 2004; 44(4): 323331.
  15. 15. Tamura G, Sato K, Akiyama S, et al. Molecular characterization of undifferentiatedtype gastric carcinoma [J]. Lab Invest, 2001; 81(4): 593598.
  16. 16. Shiao YH, Palli D, Buzard GS, et al. Implications of p53 mutation spectrum for cancer etiology in gastric cancers of various histologic types from a highrisk area of central Italy [J]. Carcinogenesis, 1998; 19 (12): 21452149.
  17. 17. Morgan C, Jenkins GJ, Ashton T, et al. Detection of p53 mutations in precancerous gastric tissue [J]. Br J Cancer, 2003; 89(7): 13141319.
  18. 18. Taguchi A, Ohmiya N, Itoh A, et al. Severity of atrophic gastritis related to antiparietal cell antibody and gastric carcinogenesis, including p53 mutations [J]. J Gastroenterol Hepatol, 2006; 21(3): 545551.
  19. 19. Azarhoush R, Keshtkar AA, Amiriani T, et al. Relationship between p53 expression and gastric cancers in cardia and antrum [J]. Arch Iran Med, 2008; 11(5): 502506.
  20. 20. Tajima Y, Yamazaki K, Makino R, et al. Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach [J]. Br J Cancer, 2007; 96(4): 631638.
  21. 21. Nayak SK, Panesar PS, Kumar H. p53Induced apoptosis and inhibitors of p53 [J]. Curr Med Chem, 2009; 16(21): 26272640.
  22. 22. Ohnishi T, Takahashi A, Mori E, et al. p53 Targeting can enhance cancer therapy via radiation, heat and anticancer agents [J]. Anticancer Agents Med Chem, 2008; 8(5): 564570.
  23. 23. Yano T, Ochiai A, Doi T, et al. Expression of HER2 in gastric cancer: Comparison between protein expression and gene amplification using a new commercial kit [J]. J Clin Oncol, 2004; 22(14S): 4053.
  24. 24. Rastelli F, Crispino S. Factors predictive of response to hormone therapy in breast cancer [J]. Tumori, 2008; 94(3): 370383.
  25. 25. Schuell B, Gruenberger T, Scheithauer W, et al. HER2/neu protein expression in colorectal cancer [J]. BMC Cancer, 2006; 6: 123127.
  26. 26. Eltze E, Wülfing C, Von Struensee D, et al. Cox2 and Her2/neu coexpression in invasive bladder cancer [J]. Int J Oncol, 2005; 26(6):15251531.
  27. 27. Sakai K, Mori S, Kawamoto T, et al. Expression of epidermal growth factor receptors on normal human gastric epithelia and gastric carcinomas [J]. J Natl Cancer Inst, 1986; 77(5): 10471052.
  28. 28. Park DI, Yun JW, Park JH, et al. HER2/neu amplification is an independent prognostic factor in gastric cancer [J]. Dig Dis Sci, 2006; 51(8): 13711379.
  29. 29. Gravalos C, Mrquez A, GarcíaCarbonero R, et al. Correlation between Her2/neu overexpression/amplification and clinicopathological parameters in advanced gastric cancer (AGC) patients (pts): A prospective study [C]. 2007 Gastrointestinal Cancers Symposium， 2007； Abstract No: 89.
  30. 30. Lordick F, Bang YJ, Kang YK, et al. HER2positive advanced gastric cancer: similar HER2positivity levels to breast cancer [J]. Eur J Cancer, 2007; 5(4): 271277.
  31. 31. Tanner M, Hollmén M, Junttila TT, et al. Amplification of HER2 in gastric carcinoma: association with Topoisomerase II gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab [J]. Ann Oncol, 2005; 16(2): 273278.
  32. 32. Nicholas G, Cripps C, Au HP, et al. Early results of a trial of trastuzumab, cisplatin and docetaxel for the treatment of metastatic gastric cancer overexpressing HER2 [J]. ESMO, 2006; 17 (Suppl 9): 316.
  33. 33. 汪劭婷, 朱朝暉, 李小毅. 胃癌新輔助化療療效臨床評(píng)價(jià)方法及進(jìn)展 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010; 17(2): 200204.
  34. 34. Sastre J, GarciaSaenz JA, DiazRubio E. Chemotherapy for gastric cancer [J]. World J Gastroenterol, 2006; 12(2): 204213.
  35. 35. Rech J, Arnold D, Folprecht G, et al. A pilot study of trastuzumab monotherapy in patients who progressed while on chemotherapy for metastatic or locally advanced HER2 positive gastric cancer [J]. ESMO, 2006; 17 (Suppl 9): 314.
  36. 36. Kim SY, Kim HP, Kim YJ, et al. Trastuzumab inhibits the growth of human gastric cancer cell lines with HER2 amplification synergistically with cisplatin [J]. Int J Oncol, 2008; 32(1): 8995.
  37. 37. MezaJunco J, Au HJ, Sawyer MB. Trastuzumab for gastric cancer [J]. Expert Opin Biol Ther, 2009; 9(12):15431551.
  38. 38. Kang Y, Bang Y, Lordick F, et al. Incidence of gastric and gastroesophageal cancer in the ToGA trial: Correlation with HER2 positivity [C]. 2008 Gastrointestinal Cancers Symposium, 2008: 75 (Abstr 11).
  39. 39. FujimotoOuchi K, Sekiguchi F, Yasuno H, et al. Antitumor activity of trastuzumab in combination with chemotherapy in human gastric cancer xenograft models [J]. Cancer Chemother Pharmacol, 2007; 59(6): 795805.
  40. 40. Van Cutsem E, Kang Y, Chung H, et al. Efficacy results from the ToGA trial: A phase Ⅲ study of trastuzumab added to standard chemotherapy (CT) in firstline human epidermal growth factor receptor 2 (HER2)positive advanced gastric cancer (GC) [J]. J Clin Oncol, 2009; 27(18S): LBA4509.