請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61646完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 許秉寧 | |
| dc.contributor.author | Cong-Hao Lai | en |
| dc.contributor.author | 賴琮皓 | zh_TW |
| dc.date.accessioned | 2021-06-16T13:08:20Z | - |
| dc.date.available | 2013-09-24 | |
| dc.date.copyright | 2013-09-24 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-01 | |
| dc.identifier.citation | Allman, D., Jain, A., Dent, A., Maile, R.R., Selvaggi, T., Kehry, M.R., and Staudt, L.M. (1996). BCL-6 expression during B-cell activation. Blood 87, 5257-5268.
Angelin-Duclos, C., Cattoretti, G., Lin, K.I., and Calame, K. (2000). Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo. J. Immunol. 165, 5462-5471. Arbibe, L., Kim, D.W., Batsche, E., Pedron, T., Mateescu, B., Muchardt, C., Parsot, C., and Sansonetti, P.J. (2007). An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses. Nat Immunol 8, 47-56. Asahi, M., Azuma, T., Ito, S., Ito, Y., Suto, H., Nagai, Y., Tsubokawa, M., Tohyama, Y., Maeda, S., Omata, M., et al. (2000). Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells. J Exp Med 191, 593-602. Backert, S., Muller, E.C., Jungblut, P.R., and Meyer, T.F. (2001). Tyrosine phosphorylation patterns and size modification of the Helicobacter pylori CagA protein after translocation into gastric epithelial cells. Proteomics 1, 608-617. Backert, S., Ziska, E., Brinkmann, V., Zimny-Arndt, U., Fauconnier, A., Jungblut, P.R., Naumann, M., and Meyer, T.F. (2000). Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus. Cell Microbiol 2, 155-164. Bhavsar, A.P., Guttman, J.A., and Finlay, B.B. (2007). Manipulation of host-cell pathways by bacterial pathogens. Nature 449, 827-834. Blaser, M.J., Perez-Perez, G.I., Kleanthous, H., Cover, T.L., Peek, R.M., Chyou, P.H., Stemmermann, G.N., and Nomura, A. (1995). Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 55, 2111-2115. Cattoretti, G., Pasqualucci, L., Ballon, G., Tam, W., Nandula, S.V., Shen, Q., Mo, T., Murty, V.V., and Dalla-Favera, R. (2005). Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice. Cancer Cell 7, 445-455. Churin, Y., Al-Ghoul, L., Kepp, O., Meyer, T.F., Birchmeier, W., and Naumann, M. (2003). Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response. J Cell Biol 161, 249-255. Covacci, A. (1999). Helicobacter pylori Virulence and Genetic Geography. Science 284, 1328-1333. Covacci, A., Telford, J.L., Del Giudice, G., Parsonnet, J., and Rappuoli, R. (1999). Helicobacter pylori virulence and genetic geography. Science 284, 1328-1333. Dent, A.L., Shaffer, A.L., Yu, X., Allman, D., and Staudt, L.M. (1997). Control of inflammation, cytokine expression, and germinal center formation by BCL-6. Science 276, 589-592. Eck, M., Schmausser, B., Haas, R., Greiner, A., Czub, S., and Muller-Hermelink, H.K. (1997). MALT-type lymphoma of the stomach is associated with Helicobacter pylori strains expressing the CagA protein. Gastroenterology 112, 1482-1486. Fischer, W., Puls, J., Buhrdorf, R., Gebert, B., Odenbreit, S., and Haas, R. (2001). Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin-8. Mol Microbiol 42, 1337-1348. Forman, D., Newell, D.G., Fullerton, F., Yarnell, J.W.G., Stacey, A.R., Wald, N., and Sitas, F. (1991). Association between infection with Helicobacter pylori and risk of gastric cancer evidence from a prospective investigation. BMJ 302, 1302-1305. Gisbert, J.P., and Calvet, X. (2011). Review article: common misconceptions in the management of Helicobacter pylori-associated gastric MALT-lymphoma. Aliment Pharmacol Ther 34, 1047-1062. Graham, D.Y., and Yamaoka, Y. (1998). H. pylori and cagA: relationships with gastric cancer, duodenal ulcer, and reflux esophagitis and its complications. Helicobacter 3, 145-151. Hatakeyama, M. (2002). Deregulation of SHP-2 tyrosine phosphatase by the Helicobacter pylori virulence factor CagA. Keio J Med 51 Suppl 2, 26-32. Hatakeyama, M. (2004). Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nat Rev Cancer 4, 688-694. Hatakeyama, M. (2008). SagA of CagA in Helicobacter pylori pathogenesis. Curr Opin Microbiol 11, 30-37. Higashi, H., Tsutsumi, R., Muto, S., Sugiyama, T., Azuma, T., Asaka, M., and Hatakeyama, M. (2002). SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 295, 683-686. Higashi, H., Yokoyama, K., Fujii, Y., Ren, S., Yuasa, H., Saadat, I., Murata-Kamiya, N., Azuma, T., and Hatakeyama, M. (2005). EPIYA motif is a membrane-targeting signal of Helicobacter pylori virulence factor CagA in mammalian cells. J Biol Chem 280, 23130-23137. Hof, P., Pluskey, S., Dhe-Paganon, S., Eck, M.J., and Shoelson, S.E. (1998). Crystal structure of the tyrosine phosphatase SHP-2. Cell 92, 441-450. Kallies, A., Hasbold, J., Tarlinton, D.M., Dietrich, W., Corcoran, L.M., Hodgkin, P.D., and Nutt, S.L. (2004). Plasma cell ontogeny defined by quantitative changes in Blimp-1 expression. J. Exp. Med. 200, 967-977. Keller, A.D., and Maniatis, T. (1991). Identification and characterization of a novel repressor of beta-interferon gene expression. Genes Dev 5, 868-879. Kodama, A., Matozaki, T., Fukuhara, A., Kikyo, M., Ichihashi, M., and Takai, Y. (2000). Involvement of an SHP-2-Rho small G protein pathway in hepatocyte growth factor/scatter factor-induced cell scattering. Mol Biol Cell 11, 2565-2575. Kwon, M.S., Go, J.H., Choi, J.S., Lee, S.S., Ko, Y.H., Rhee, J.C., and Ree, H.J. (2003). Critical evaluation of Bcl-6 protein expression in diffuse large B-cell lymphoma of the stomach and small intestine. Am J Surg Pathol 27, 790-798. Lee, J.H., Jun, S.H., Baik, S.C., Kim, D.R., Park, J.Y., Lee, Y.S., Choi, C.H., and Lee, J.C. (2012). Prediction and screening of nuclear targeting proteins with nuclear localization signals in Helicobacter pylori. J Microbiol Methods 91, 490-496. Lin, W.C., Tsai, H.F., Kuo, S.H., Wu, M.S., Lin, C.W., Hsu, P.I., Cheng, A.L., and Hsu, P.N. (2010). Translocation of Helicobacter pylori CagA into Human B lymphocytes, the origin of mucosa-associated lymphoid tissue lymphoma. Cancer Res 70, 5740-5748. Marshall, B.J., and Warren, J.R. (1984). Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1, 1311-1315. Matangkasombut, O., Wattanawaraporn, R., Tsuruda, K., Ohara, M., Sugai, M., and Mongkolsuk, S. (2010). Cytolethal distending toxin from Aggregatibacter actinomycetemcomitans induces DNA damage, S/G2 cell cycle arrest, and caspase- independent death in a Saccharomyces cerevisiae model. Infect Immun 78, 783-792. Matysiak-Budnik, T., and Megraud, F. (2006). Helicobacter pylori infection and gastric cancer. Eur J Cancer 42, 708-716. McSweeney, L.A., and Dreyfus, L.A. (2004). Nuclear localization of the Escherichia coli cytolethal distending toxin CdtB subunit. Cell Microbiol 6, 447-458. Mimuro, H., Suzuki, T., Tanaka, J., Asahi, M., Haas, R., and Sasakawa, C. (2002). Grb2 is a key mediator of helicobacter pylori CagA protein activities. Mol Cell 10, 745-755. Mueller, D., Tegtmeyer, N., Brandt, S., Yamaoka, Y., De Poire, E., Sgouras, D., Wessler, S., Torres, J., Smolka, A., and Backert, S. (2012). c-Src and c-Abl kinases control hierarchic phosphorylation and function of the CagA effector protein in Western and East Asian Helicobacter pylori strains. J Clin Invest 122, 1553-1566. Niu, H., Cattoretti, G., and Dalla-Favera, R. (2003). BCL6 controls the expression of the B7-1/CD80 costimulatory receptor in germinal center B cells. J Exp Med 198, 211-221. Nomura, A.M., Perez-Perez, G.I., Lee, J., Stemmermann, G., and Blaser, M.J. (2002). Relation between Helicobacter pylori cagA status and risk of peptic ulcer disease. Am J Epidemiol 155, 1054-1059. Odenbreit, S., Puls, J., Sedlmaier, B., Gerland, E., Fischer, W., and Haas, R. (2000). Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287, 1497-1500. Ohnishi, N., Yuasa, H., Tanaka, S., Sawa, H., Miura, M., Matsui, A., Higashi, H., Musashi, M., Iwabuchi, K., Suzuki, M., et al. (2008). Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci U S A 105, 1003-1008. Parsonnet, J., and Isaacson, P.G. (2004). Bacterial infection and MALT lymphoma. N Engl J Med 350, 213-215. Peek, R.M., Jr., and Blaser, M.J. (2002). Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer 2, 28-37. Peng, H., Ranaldi, R., Diss, T.C., Isaacson, P.G., Bearzi, I., and Pan, L. (1998). High frequency of CagA+ Helicobacter pylori infection in high-grade gastric MALT B-cell lymphomas. J Pathol 185, 409-412. Pennini, M.E., Perrinet, S., Dautry-Varsat, A., and Subtil, A. (2010). Histone methylation by NUE, a novel nuclear effector of the intracellular pathogen Chlamydia trachomatis. PLoS Pathog 6, e1000995. Phan, R.T., and Dalla-Favera, R. (2004). The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. Nature 432, 635-639. Polk, D.B., and Peek, R.M., Jr. (2010). Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer 10, 403-414. Rohde, M., Puls, J., Buhrdorf, R., Fischer, W., and Haas, R. (2003). A novel sheathed surface organelle of the Helicobacter pylori cag type IV secretion system. Mol Microbiol 49, 219-234. Rugge, M., Busatto, G., Cassaro, M., Shiao, Y.H., Russo, V., Leandro, G., Avellini, C., Fabiano, A., Sidoni, A., and Covacci, A. (1999). Patients Younger than 40 Years with Gastric Carcinoma. Cancer 85, 2506-2511. Schoenwaelder, S.M., Petch, L.A., Williamson, D., Shen, R., Feng, G.S., and Burridge, K. (2000). The protein tyrosine phosphatase Shp-2 regulates RhoA activity. Curr Biol : CB 10, 1523-1526. Shaffer, A.L., Yu, X., He, Y., Boldrick, J., Chan, E.P., and Staudt, L.M. (2000). BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control. Immunity 13, 199-212. Shapiro-Shelef, M., Lin, K.I., McHeyzer-Williams, L.J., Liao, J., McHeyzer-Williams, M.G., and Calame, K. (2003). Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells. Immunity 19, 607-620. Sheu, B.S., Yang, H.B., Wu, J.J., Huang, A.H., Lin, X.Z., and Su, I.J. (1999). Development of Helicobacter pylori infection model in BALB/c mice with domestic cagA-positive and -negative strains in Taiwan. Dig Dis Sci 44, 868-875. Stein, M., Rappuoli, R., and Covacci, A. (2000). Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. Proc Natl Acad Sci U S A 97, 1263-1268. Stein, M., Bagnoli, F., Halenbeck, R., Rappuoli, R., Fantl, W.J., and Covacci, A. (2002). c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs. Mol. microbiol 43, 971-980 Tunyaplin, C., Shaffer, A.L., Angelin-Duclos, C.D., Yu, X., Staudt, L.M., and Calame, K.L. (2004). Direct repression of prdm1 by Bcl-6 inhibits plasmacytic differentiation. J Immunol 173, 1158-1165. Tunyaplin, C., Shapiro, M.A., and Calame, K.L. (2000). Characterization of the B lymphocyte-induced maturation protein-1 (Blimp-1) gene, mRNA isoforms and basal promoter. Nucleic Acids Res 28, 4846-4855. Vasanwala, F.H., Kusam, S., Toney, L.M., and Dent, A.L. (2002). Repression of AP-1 function: a mechanism for the regulation of Blimp-1 expression and B lymphocyte differentiation by the B cell lymphoma-6 protooncogene. J Immunol 169, 1922-1929. Wang, X., Li, Z., Naganuma, A., and Ye, B.H. (2002). Negative autoregulation of BCL-6 is bypassed by genetic alterations in diffuse large B cell lymphomas. Proc Natl Acad Sci U S A 99, 15018-15023. Wotherspoon, A.C., Doglioni, C., Diss, T.C., Pan, L., Moschini, A., de Boni, M., and Isaacson, P.G. (1993). Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 342, 575-577. Ye, B.H., Rao, P.H., Chaganti, R.S., and Dalla-Favera, R. (1993). Cloning of bcl-6, the locus involved in chromosome translocations affecting band 3q27 in B-cell lymphoma. Cancer Res 53, 2732-2735. Ye, B.H., Cattoretti, G., Shen, Q., Zhang, J., Hawe, N., de Waard, R., Leung, C., Nouri-Shirazi, M., Orazi, A., Chaganti, R.S., et al. (1997). The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation. Nat. Genet. 16, 161-170. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61646 | - |
| dc.description.abstract | 胃幽門螺旋桿菌 (Helicobacter pylori) 首先在患有胃炎以及胃潰瘍的病患胃部所發現，其可造成慢性胃炎、胃潰瘍、胃黏膜相關淋巴組織淋巴癌以及胃癌等疾病，在胃幽門螺旋桿菌所產生的蛋白中，CagA 被認為是主要的毒性蛋白，而CagA 是一個 125-145 kDa 的蛋白質，當胃幽門螺旋桿菌附著上胃上皮細胞後，利用編碼在 Cag PAI 上的第四型分泌系統 (type VI secretion system) 或其他分子送入到胃上皮細胞中，進一步被細胞中的磷酸酶 Src family kinase 和 c-Abl磷酸酶磷酸化，形成 phospho-CagA 和 SHP-2 結合，進而活化 SHP-2，從而改變細胞與細胞間的附著、細胞型態的改變以及細胞的遷移。SHP-2 不正常持續的活化情形也和癌症的生成有關，CagA 在胃上皮細胞內會加速細胞週期，刺激細胞增生。另一方面，具有CagA基因的胃幽門螺旋桿菌也與 low-grade gastritis mucosa associated lymphoid tissue (MALT) lymphoma 的形成有關，之前實驗室所發表的論文也證明 CagA 可以經由第四型分泌系統送入 B 細胞中並活化 MAP kinase 分子─ERK 與 P38，以及增加抗細胞凋亡分子 BCL-2 和 BCL-XL 的表現，在 MALT lymphoma 生成中，CagA 和 B 細胞的直接作用可能扮演抗細胞凋亡並促進細胞增生的角色。
目前對於 CagA在細胞內的位置及作用仍不清楚，我們進一步探討 CagA進入細胞後的分布以及磷酸化對其影響。我們以 B 細胞和胃幽門螺旋桿菌共同培養並且使用核質分離的技術，觀察到 CagA 確實可存在於細胞質和細胞核中，而且隨時間增加進入核內的 CagA 有增加的現象，細胞核內的 CagA 或是phospho-CagA 較細胞質能有更持續的表現，此現象可能代表 CagA 在核內的具有其生理意義進而影響細胞的生存或活化。接著我們再製作不同 N 端 truncate 片段的 CagA 質體 DNA 轉染進 AGS 細胞中，觀察 CagA 進核的方式，我們發現到 N 端 600-892 a.a.對於 CagA 進入細胞核有重要的角色。在 B 細胞分化上，我們觀察到胃幽門螺旋桿菌可使 B 細胞內 BCL-6 蛋白質表現量下降，然而在CagA 基因剔除的菌株中，BCL-6 並無明顯下降。利用 Real-time PCR 測量 BCL-6 mRNA 表現，也發現 BCL-6 mRNA 表現受到抑制，但是在 CagA 基因剔除菌株共同培養的組別並未發現相同結果。與漿細胞分化相關的轉錄分子 BLIMP-1，利用 Western blot 以及 Real-time PCR 我們也觀察到和BCL-6相反的表現，蛋白量和mRNA 都有明顯提升，在 CagA 基因剔除菌株共同培養的組別則無此現象。這些結果顯示 CagA 被胃幽門螺旋桿菌送入 B 細胞可以使 BCL-6表現下降，BLIMP-1表現上升。我們的研究結果顯示這些分子的表現可能和 CagA在 B 細胞內的位置有關並可能參與胃幽門螺旋桿菌造成胃黏膜相關淋巴組織淋巴瘤的形成。期待未來的研究結果能進一步釐清 CagA 誘導 B 淋巴細胞的活化或 MALT lymphoma 的形成有重要的啟發與貢獻。 | zh_TW |
| dc.description.abstract | Abstract
Helicobacter pylori was first discovered in the stomach of patients with gastritis and gastric ulcer and is linked to the development of chronic gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. In proteins produced by Helicobacter pylori, CagA is considered as the major virulent protein about 125-145 kDa and can be injected through T4SS (type four secretion system) and other molecules encoded on CagPAI into gastric epithelial cell when Helicobacter pylori contact with gastric epithelial cell. The CagA protein in gastric epithelial cell is further phosphorylated by Src family kinase and c-Abl. Phospho-CagA binds with SHP-2 and activates SHP-2 in a phosphorylation dependent manner. Activated SHP-2 can change actin filament structure resulting in cell-cell adhesion, cell phenotype and migration alternation. SHP-2 deregulation associates with cancer formation. CagA in gastric epithelial cell could accelerate cell cycle and stimulate cell proliferation. On the other hand, CagA+ Helicobacter pylori is associates with low-grade gastritis mucosa-associated lymphoid tissue (MALT) lymphoma formation. Previous study showed that CagA can be injected through T4SS into B cells and activate MAP kinase─ERK and P38 along with increased anti-apoptosis molecule BCL-2 and BCL-XL expression. In MALT lymphoma genesis, CagA directly interacts with B cells may contribute to anti-apoptosis and promoting proliferation in B cells. By now, CagA intracellular localization and function are currently unknown. We further investigated distribution of translocated CagA in cells and phosphorylation effect on distribution. So far, we co-cultured B cells with H. pylori then applied to Nucleocytoplasmic separation and observed that CagA localize in cytosol and nucleus and nucleus CagA persist longer than cytosol CagA. CagA nucleus localization may represent some biological mechanism so as to affecting B cells survival or activation. Next, we use N-terminal truncate CagA transfected into AGS cells study which sequence or motif is required for translocation and we find that there is no significant difference in N-terminal truncate CagA except lacking CagA 600-892 a.a.. In B cell differentiation, we also found that H. pylori decreases BCL-6 protein expression, but BCL-6 does not decrease when BJAB cells co-cultures with CagA knock-out strain. Using Real-time PCR to investigate BCL-6 mRNA expression, we find that expression of BCL-6 mRNA is inhibited, but not in BJAB cells co-cultures with CagA knock-out strain. We used Western blot and Real-time PCR to explore whether H. pylori can affect the expression of plasma cell differentiation associated molecule and find that in contrast to BCL-6, BLIMP-1 protein and mRNA increase in co-culture with H. pylori but not with CagA knock-out strain. Our research results indicate that CagA in BJAB cells down-regulate BCL-6 and up-regulate BLIMP-1 which expression may associate with CagA localization in BJAB cells and lead to MALT lymphoma formation. Our results in this study may provide an inspiration and contribution on CagA-induced B cells activation/differentiation or MALT lymphoma genesis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T13:08:20Z (GMT). No. of bitstreams: 1 ntu-102-R00449002-1.pdf: 4807380 bytes, checksum: 22464dd0c88b33692e7b8eb936ee3ab6 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 目錄
致謝 ii 中文摘要 iii Abstract v 研究背景 1 1.胃幽門螺旋桿菌簡介 1 2.CagA 與第四型分泌系統 2 3.CagA phosphorylation 和 SHP-2 2 4.CagA 與 MALT lymphoma 3 5.CagA 可以 translocate 至 B 細胞 3 6.CagA 在胃上皮細胞 AGS 以及 B 細胞中的分布 4 7.BCL-6 5 8.BLIMP-1 5 研究動機與目的 7 實驗方法與材料 8 實驗方法 8 實驗材料 13 實驗結果 19 1.胃幽門螺旋桿菌 CagA 進入 B 細胞和 AGS 細胞的細胞質和細胞核中 19 2.胃幽門螺旋桿菌 CagA 存在於在真核細胞的細胞質和細胞核中且有不同的動態 20 3.CagA進入細胞核依賴特定片段 21 4.胃幽門螺旋桿菌可藉由 CagA 降低 B 細胞內 BCL-6 並提高 BLIMP-1 的表現。 22 結果討論 23 1.胃幽門螺旋桿菌CagA進入B細胞和AGS細胞的細胞質和細胞核中 23 2.CagA在細胞核內可能的角色 24 3.CagA 600-892胺基酸存在未知 NLS 或 tyrosine 磷酸化位置 25 4.胃幽門螺旋桿菌可藉由 CagA 降低 B 細胞內 Bcl-6並提高 Blimp-1的表現 26 5.結論 27 參考文獻 28 圖表說明 39 | |
| dc.language.iso | zh-TW | |
| dc.title | 胃幽門螺旋桿菌 CagA 分子在細胞內的分布與誘導 B 細胞活化/分化的角色之研究 | zh_TW |
| dc.title | Study of H. pylori CagA intracellular localization and induction of B cell activation/differentiation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 謝世良,林國儀,周祖述 | |
| dc.subject.keyword | 胃幽門螺旋桿菌,CagA,細胞內分布,活化/分化, | zh_TW |
| dc.subject.keyword | Helicobacter pylori,CagA,intracellular localization,activation/differenciation, | en |
| dc.relation.page | 50 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-08-01 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-102-1.pdf 目前未授權公開取用 | 4.69 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。