跳到主要內容

臺灣博碩士論文加值系統

(44.210.149.205) 您好!臺灣時間:2024/04/16 19:09
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:洪慧珊
研究生(外文):Huey-Shan Hung
論文名稱:抗凋亡蛋白在廚房油煙誘發肺腺癌細胞存活與增生之角色研究
論文名稱(外文):The Role of Inhibitory of Apoptosis Proteins in Lung Adenocarcinoma Cell Survival and Proliferation Induced by Cooking Oil Fumes
指導教授:李輝李輝引用關係張基隆張基隆引用關係
指導教授(外文):Huei LeeKee-Lung Chang
學位類別:博士
校院名稱:高雄醫學大學
系所名稱:醫學研究所博士班
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:2005
畢業學年度:94
語文別:中文
論文頁數:134
中文關鍵詞:廚房油煙抗凋亡蛋白肺腺癌細胞
外文關鍵詞:lung adenocarcinoma cellinhibitory of apoptosis proteinscooking oil fumes
相關次數:
  • 被引用被引用:4
  • 點閱點閱:392
  • 評分評分:
  • 下載下載:81
  • 收藏至我的研究室書目清單書目收藏:2
文獻指出廚房油煙 (cooking oil fumes, COF) 暴露與台灣女性肺癌發生有關。本研究室先前之研究結果指出,COF會經由活化NF-κB路徑,誘發肺腺癌細胞Cox-2基因過度表現,而NF-κB路徑活化能影響腫瘤細胞之存活,因此假設長時間暴露COF可能會促進肺腫瘤細胞的增生。本研究以肺腺癌 A549細胞為研究模式,探討COF 是否確實會誘發肺癌細胞存活與生長,並了解其可能之分子機轉。首先於MTT (3-(4,5-dimethyl thiazol-2-yl)-2,5- diphenyl-tetrazolium bromide) 之細胞存活實驗中發現,當細胞處理COF 48小時後會增加細胞之存活率,而流式細胞細胞儀之結果亦顯示COF暴露會增加細胞 S phase之分佈比率。西方點墨法之結果顯示,IAP2蛋白會隨著COF濃度增高,增強IAP2 (inhibitory of antiapoptosis protein 2) 蛋白的表現量。當同時處理NF-κB抑制劑 BAY,則會阻斷COF誘導IAP2蛋白之能力。這顯示NF-κB 路徑可能參與 COF 誘導IAP2蛋白之表現。COF除了會誘導IAP2表現外,是否亦會誘發其他三種IAPs 蛋白的表現(IAP1、survivin以及XIAP)?這些蛋白之表現與COF所誘導肺腺癌細胞增生是否有關?結果顯示,IAP1,IAP2及 survivin蛋白會分別被 COF, BaP,及2,4-DDE誘導而表現,其中以IAP2蛋白之誘導表現較強。而XIAP的表現卻會被 COF及2,4-DDE抑制,但不會被BaP影響。雖然COF對IAP2及XIAP之表現有相反之作用,但是COF仍然會抑制凋亡蛋白 caspase-3 之活性,而使細胞存活與增生。因此爲了反應實際生活中,台灣婦女暴露COF引起女性肺癌之可能機轉,本研究即以COF混合物來探討誘發IAP2的可能參與之訊號路徑。首先將三種不同訊息路徑之抑制劑(SB203580,PD98059,LY294002)分別與COF同時處理細胞,IAP2 蛋白表現可被PI3K 之抑制劑LY294002 抑制,而SB203580 (p38) 及PD98059 (ERK) 則無此能力。在細胞週期 sub-G1 phase 與 TUNEL assay 之結果顯示,LY294002 會促進肺癌細胞之凋亡,因此除了 NF-κB路徑之外,PI3K在COF所誘導肺腺癌細胞增生與存活可能亦扮演重要之角色。爲了解COF誘導A549細胞增生,是否與細胞週期相關之調控蛋白有關,本研究同樣以西方墨點法得知,COF確實會促進cyclin D1的表現,卻會顯著抑制p21蛋白的表現。由以上之結果得知,活化 IAP1, IAP2, survivin 以及cyclin D1蛋白之表現與抑制 XIAP,caspase-3,以及p21蛋白之表現,可部份解釋COF誘導肺腺癌細胞之存活與增生的分子機轉。至於COF引起肺癌細胞增生是否與ROS產生有關?本研究以DCF-dA分析ROS之形成,發現COF處理肺腺癌細胞會產生ROS,並發現COF所誘導ROS之產生可能是經由PI3K活化,進而誘導p-Akt之表現,促進肺腺細胞之增生。總結,本研究結果發現COF暴露會促進肺腺癌細胞之存活與增生,有助於了解廚房油煙暴露與台灣女性肺癌的形成之分子機轉,在台灣不抽菸女性肺癌之預防與治療策略上提供學理之參考及助益。
Cooking oil fumes (COF) exposure was demonstrated to be associated with lung cancer development in Taiwanese nonsmoking women. Previous studies showed that Cox-2 overexpression and oxidative DNA damage were observed in CL-3 lung adenocarcinoma cells after exposed to COF. Involvement of COF in lung tumorigenesis might be mediated through induction of IAPs family protein expressions to cause cell survival and proliferation. To test the hypothesis, A549 lung adenocarcinoma cell line was used in this study. After the cells exposed to various concentrations of COF for 48 hr, the cell viability of A549 was unexpectedly increased in a concentration-dependent manner based on MTT assay. In addition, flow cytometery data showed that the proportion of A549 cells at S-phase was markedly increased after exposure of COF. To elucidate whether the antiapoptotic c-IAP2 (IAP2) was involved in COF-improved cell survival, Western blot data indicated that IAP2 protein level was significantly induced by COF in a concentration-dependent manner. Moreover, the effect of BAY, a NF-κB binding inhibitor, on the COF-induced IAP2 protein level was shown that NF-κB activation by COF may partly be involved in IAP2 induction. Thus, the positive impact of COF on cell survival and proliferation of A549 lung tumor cells may be result in induction of IAP2 overexpression at least in part through NF-κB signaling pathway. To verify whether other antiapoptotic proteins were also associated with lung cancer cell survival and proliferation, other IAP family proteins, including IAP1, XIAP and survivin expressions, were evaluated by Western blotting after the cells were treated with COF and its two components, BaP and 2,4-DDE. Our data show that IAP1 and survivin expression levels were increased by COF, BaP, and 2,4-DDE, but not like IAP2 induction in a dose-dependent manner. On the contrary, XIAP surprisingly was decreased by COF and 2,4-DDE, but not by BaP. Even though there were different effects of COF on IAP2 and XIAP protein expressions, the expression of apoptotic caspase-3 was diminished by COF. Therefore, to mimic the effects of exposure to a complex mixture of COF on Chinese female lung cancer development, the role of IAPs attenuated by COF on lung cancer cell proliferation was investigated. To verify which signaling pathway was responsible for IAP2 induction four inhibitors, SB203580 (p38 MAPK), PD98059 (ERK), BAY (NF-κB), and LY294002 (PI3K), were added to the A549 cells. IAP2 expressions induced by COF were abolished by the additions of BAY and LY294002, but not affected by SB203580 and PD98059 treatments, suggesting that IAP2 induction by COF may be mediated through the NF-κB and PI3K pathways. To further verify the role of both pathways in IAP2 induction by COF, the down-stream Akt and phospho-Akt (p-Akt) protein expressions were also determined by Western blotting after the cells were concomitantly treated with BAY and LY294002. Our data demonstrate that p-Akt expression increased with COF treatment and the expression level decreased with the addition of LY294002, but not by BAY. These results suggest that the PI3K pathway might play a more direct role in the IAP2 induction by COF. The effect of COF on the cell cycle of A549 cells was further investigated by flow cytometry. The proportion of the S-phase of A549 cells increased significantly with the COF treatment. Additionally, we also show that the cell cycle regulation involved in A549 cell proliferation is associated with induction of cyclin D1 and reduction of p21Cip1/Waf1 protein expression. Taken together, increases of IAP1, IAP2, survivin and cyclin D1 expressions and decreases of XIAP, caspase-3, and p21 expressions might partly contribute to lung cancer cell survival and proliferation after COF exposure.
壹:中文摘要……………………………………………………………3
貳:英文摘要……………………………………………………………6
叁:縮寫表………………………………………………………………9
肆:文獻回顧……………………………………………………………11
伍:緒言…………………………………………………………………26
陸:材料與方法…………………………………………………………31
柒:結果…………………………………………………………………47
捌:討論…………………………………………………………………98
玖:結論…………………………………………………………………110
拾:參考文獻……………………………………………………………112
Andersen, M.H., Pedersen, L.O., Capeller, B., Brocker, E.B., Becker, J.C. and thor Straten, P. (2001) Spontaneous cytotoxic T-cell responses against survivin-derived MHC class I-restricted T-cell epitopes in situ as well as ex vivo in cancer patients. Cancer Res, 61, 5964-5968.

Bandala, E., Espinosa, M., Maldonado, V. and Melendez-Zajgla, J. (2001) Inhibitor of apoptosis-1 (IAP-1) expression and apoptosis in non-small-cell lung cancer cells exposed to gemcitabine. Biochem Pharmacol, 62, 13-19.

Berg, I., Overvik, E., Nord, C.E. and Gustafsson, J.A. (1988) Mutagenic activity in smoke formed during broiling of lean pork at 200, 250 and 300 degrees C. Mutat Res, 207, 199-204.

Bianco, R., Shin, I., Ritter, C.A., Yakes, F.M., Basso, A., Rosen, N., Tsurutani, J., Dennis, P.A., Mills, G.B. and Arteaga, C.L. (2003) Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors. Oncogene, 22, 2812-2822.

Black, M.J. and Brandt, R.B. (1974) Spectrofluorometric analysis of hydrogen peroxide. Anal Biochem, 58, 246-254.

Boehle, A.S., Kurdow, R., Boenicke, L., Schniewind, B., Faendrich, F., Dohrmann, P. and Kalthoff, H. (2002) Wortmannin inhibits growth of human non-small-cell lung cancer in vitro and in vivo. Langenbecks Arch Surg, 387, 234-239.

Brownson, R.C., Chang, J.C. and Davis, J.R. (1992) Gender and histologic type variations in smoking-related risk of lung cancer. Epidemiology, 3, 61-64.

Bush, J.A., Cheung, K.J., Jr. and Li, G. (2001) Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53. Exp Cell Res, 271, 305-314.

Carter, B.Z., Wang, R.Y., Schober, W.D., Milella, M., Chism, D. and Andreeff, M. (2003) Targeting Survivin expression induces cell proliferation defect and subsequent cell death involving mitochondrial pathway in myeloid leukemic cells. Cell Cycle, 2, 488-493

Cavalieri, E.L. and Rogan, E.G. (1992) The approach to understanding aromatic hydrocarbon carcinogenesis. The central role of radical cations in metabolic activation. Pharmacol Ther, 55, 183-199.

Chang, G.C., Hsu, S.L., Tsai, J.R., Liang, F.P., Lin, S.Y., Sheu, G.T. and Chen, C.Y. (2004) Molecular mechanisms of ZD1839-induced G1-cell cycle arrest and apoptosis in human lung adenocarcinoma A549 cells. Biochem Pharmacol, 68, 1453-1464.

Chauhan, D., Hideshima, T., Rosen, S., Reed, J.C., Kharbanda, S. and Anderson, K.C. (2001) Apaf-1/cytochrome c-independent and Smac-dependent induction of apoptosis in multiple myeloma (MM) cells. J Biol Chem, 276, 24453-24456.
Chen, C.J., Wu, H.Y., Chuang, Y.C., Chang, A.S., Luh, K.T., Chao, H.H., Chen, K.Y., Chen, S.G., Lai, G.M., Huang, H.H. (1990) Epidemiologic characteristics and multiple risk factors of lung cancer in Taiwan. Anticancer Res, 10, 971-976.

Chen, F., Bower, J., Leonard, S.S., Ding, M., Lu, Y., Rojanasakul, Y., Kung, H.F., Vallyathan, V., Castranova, V. and Shi, X. (2002) Protective roles of NF-kappa B for chromium(VI)-induced cytotoxicity is revealed by expression of Ikappa B kinase-beta mutant. J Biol Chem, 277, 3342-3349.

Chen, X., Kandasamy, K. and Srivastava, R.K. (2003) Differential roles of RelA (p65) and c-Rel subunits of nuclear factor kappa B in tumor necrosis factor-related apoptosis-inducing ligand signaling. Cancer Res, 63, 1059-1066.

Cheng, Y.W., Hsieh, L.L., Lin, P.P., Chen, C.P., Chen, C.Y., Lin, T.S., Su, J.M. and Lee, H. (2001) Gender difference in DNA adduct levels among nonsmoking lung cancer patients. Environ Mol Mutagen, 37, 304-310.

Cheng, YW. and Lee, H. (2003) Environmental exposure and lung cancer among nonsmokers: an example of Taiwanese female lung cancer. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, 21, 1-28.

Cherng, S.H., Huang, K.H., Yang, S.C., Wu, T.C., Yang, J.L. and Lee, H. (2002) Human 8-oxoguanine DNA glycosylase 1 mRNA expression as an oxidative stress exposure biomarker of cooking oil fumes. J Toxicol Environ Health A, 65, 265-278.

Cherpillod, P. and Amstad, P.A. (1995) Benzo[a]pyrene-induced mutagenesis of p53 hot-spot codons 248 and 249 in human hepatocytes. Mol Carcinog, 13, 15-20.

Chiang, T.A., Wu, P.F., Wang, L.F., Lee, H., Lee, C.H. and Ko, Y.C. (1997) Mutagenicity and polycyclic aromatic hydrocarbon content of fumes from heated cooking oils produced in Taiwan. Mutat Res, 381, 157-161.

Chiang, T.A., Wu, P.F. and Ko, Y.C. (1998) Prevention of exposure to mutagenic fumes produced by hot cooking oil in Taiwanese kitchens. Environ Mol Mutagen, 31, 92-96.

Chu, Z.L., McKinsey, T.A., Liu, L., Gentry, J.J., Malim, M.H. and Ballard, D.W. (1997) Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-kappaB control. Proc Natl Acad Sci U S A, 94, 10057-10062.

Cole, P., Hoover, R. and Friedell, G.H. (1972) Occupation and cancer of the lower urinary tract. Cancer, 29, 1250-1260.

Cummins, J.M., Kohli, M., Rago, C., Kinzler, K.W., Vogelstein, B. and Bunz, F. (2004) X-linked inhibitor of apoptosis protein (XIAP) is a nonredundant modulator of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in human cancer cells. Cancer Res, 64, 3006-3008.

Denissenko, M.F., Pao, A., Tang, M. and Pfeifer, G.P. (1996) Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspots in P53. Science, 274, 430-432.

Denlinger, C.E., Rundall, B.K., Keller, M.D. and Jones, D.R. (2004) Proteasome inhibition sensitizes non-small-cell lung cancer to gemcitabine-induced apoptosis. Ann Thorac Surg, 78, 1207-1214; discussion 1207-1214.

Department of Health, Executive Yuan, Republic of China. (1996) Public Health in Taiwan area. Chinese J. Prev. Med, 19, 271-274.

Deveraux, Q.L., Takahashi, R., Salvesen, G.S. and Reed, J.C. (1997) X-linked IAP is a direct inhibitor of cell-death proteases. Nature, 388, 300-304.

Deveraux, Q.L. and Reed, J.C. (1999) IAP family proteins--suppressors of apoptosis. Genes Dev, 13, 239-252.

Dickson, R.I. (1981) Nasopharyngeal carcinoma: an evaluation of 209 patients. Laryngoscope, 91, 333-354.

Dipple, A., Pigott, M.A., Agarwal, S.K., Yagi, H., Sayer, J.M. and Jerina, D.M. (1987) Optically active benzo[c]phenanthrene diol epoxides bind extensively to adenine in DNA. Nature, 327, 535-536.

Dong-Yun, S., Yu-Ru, D., Shan-Lin, L., Ya-Dong, Z. and Lian, W. (2003) Redox stress regulates cell proliferation and apoptosis of human hepatoma through Akt protein phosphorylation. FEBS Lett, 542, 60-64.

Dubrow, R. and Wegman, D.H. (1984) Cancer and occupation in Massachusetts: a death certificate study. Am J Ind Med, 6, 207-230.

Duckett, C.S., Nava, V.E., Gedrich, R.W., Clem, R.J., Van Dongen, J.L., Gilfillan, M.C., Shiels, H., Hardwick, J.M. and Thompson, C.B. (1996) A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. Embo J, 15, 2685-2694.

Dunn, B.P., and Stich, H.F. (1986)32p-postlabelling analysis of aromatic DNA addducts in human oral mucosal cells. Carcinogenesis, 11, 11-15.

Everson, R.B., Randerath, E., Santella, R.M., Cefalo, R.C., Avitts, T.A. and Randerath, K. (1986) Detection of smoking-related covalent DNA adducts in human placenta. Science, 231, 54-57.

Ferguson, H.A., Marietta, P.M. and Van Den Berg, C.L. (2003) UV-induced apoptosis is mediated independent of caspase-9 in MCF-7 cells: a model for cytochrome c resistance. J Biol Chem, 278, 45793-45800.

Ferreira, C.G., van der Valk, P., Span, S.W., Ludwig, I., Smit, E.F., Kruyt, F.A., Pinedo, H.M., van Tinteren, H. and Giaccone, G. (2001) Expression of X-linked inhibitor of apoptosis as a novel prognostic marker in radically resected non-small cell lung cancer patients. Clin Cancer Res, 7, 2468-2474.

Frost, M., Jarboe, E.A., Orlicky, D., Gianani, R., Thompson, L.C., Enomoto, T. and Shroyer, K.R. (2002) Immunohistochemical localization of survivin in benign cervical mucosa, cervical dysplasia, and invasive squamous cell carcinoma. Am J Clin Pathol, 117, 738-744.
Fulda, S., Wick, W., Weller, M. and Debatin, K.M. (2002) Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nat Med, 8, 808-815.

Galvan, V., Kurakin, A.V. and Bredesen, D.E. (2004) Interaction of checkpoint kinase 1 and the X-linked inhibitor of apoptosis during mitosis. FEBS Lett, 558, 57-62.

Gao, N., Ding, M., Zheng, J.Z., Zhang, Z., Leonard, S.S., Liu, K.J., Shi, X. and Jiang, B.H. (2002) Vanadate-induced expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor through phosphatidylinositol 3-kinase/Akt pathway and reactive oxygen species. J Biol Chem, 277, 31963-31971.

Gao, N., Zhang, Z., Jiang, B.H. and Shi, X. (2003) Role of PI3K/AKT/mTOR signaling in the cell cycle progression of human prostate cancer. Biochem Biophys Res Commun, 310, 1124-1132.

Gao, N., Shen, L., Zhang, Z., Leonard, S.S., He, H., Zhang, X.G., Shi, X. and Jiang, B.H. (2004) Arsenite induces HIF-1alpha and VEGF through PI3K, Akt and reactive oxygen species in DU145 human prostate carcinoma cells. Mol Cell Biochem, 255, 33-45.

Gao, Y.T., Blot, W.J., Zheng, W., Ershow, A.G., Hsu, C.W., Levin, L.I., Zhang, R. and Fraumeni, J.F., Jr. (1987) Lung cancer among Chinese women. Int J Cancer, 40, 604-609.

Gao, Y.T., Blot, W.J., Zheng, W., Fraumeni, J.F. and Hsu, C.W. (1988) Lung cancer and smoking in Shanghai. Int J Epidemiol, 17, 277-280.
Gordon, G.J., Appasani, K., Parcells, J.P., Mukhopadhyay, N.K., Jaklitsch, M.T., Richards, W.G., Sugarbaker, D.J. and Bueno, R. (2002) Inhibitor of apoptosis protein-1 promotes tumor cell survival in mesothelioma. Carcinogenesis, 23, 1017-1024.

Greenblatt, M.S., Bennett, W.P., Hollstein, M. and Harris, C.C. (1994) Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res, 54, 4855-4878.

Guo, J., Verma, U.N., Gaynor, R.B., Frenkel, E.P. and Becerra, C.R. (2004) Enhanced chemosensitivity to irinotecan by RNA interference-mediated down-regulation of the nuclear factor-kappaB p65 subunit. Clin Cancer Res, 10, 3333-3341.

Gupta, A.K., Soto, D.E., Feldman, M.D., Goldsmith, J.D., Mick, R., Hahn, S.M., Machtay, M., Muschel, R.J. and McKenna, W.G. (2004) Signaling pathways in NSCLC as a predictor of outcome and response to therapy. Lung, 182, 151-162.

Guzey, M., Kitada, S. and Reed, J.C. (2002) Apoptosis induction by 1alpha,25-dihydroxyvitamin D3 in prostate cancer. Mol Cancer Ther, 1, 667-677.

Halliwill, B., and Skjoldebrand, C. (1983) Heat and mass transport in solid foods. Development in Food Preservation, 2, 61-94.

Harborne, J.B. (1986) Nature, distribution and function of plant flavonoids. Prog Clin Biol Res, 213, 15-24.
Hargraves, W.A., and Pariza, M.W. (1984) Mutagens in cooked foods. J Environ Sci Health, C2, 1-49.

Harlin, H., Reffey, S.B., Duckett, C.S., Lindsten, T. and Thompson, C.B. (2001) Characterization of XIAP-deficient mice. Mol Cell Biol, 21, 3604-3608.

Hasegawa, T., Suzuki, K., Sakamoto, C., Ohta, K., Nishiki, S., Hino, M., Tatsumi, N. and Kitagawa, S. (2003) Expression of the inhibitor of apoptosis (IAP) family members in human neutrophils: up-regulation of cIAP2 by granulocyte colony-stimulating factor and overexpression of cIAP2 in chronic neutrophilic leukemia. Blood, 101, 1164-1171.

Hederson, B.E., and Louie, E. (1978) Discussion of risk factors for nasopharyneal carcinoma. In:"Nasopharyngeal Carcinoma: Etiology and Control" (deThe G., Ito Y., and Davis W., eds), IARC Scientific Publication No.20. International Agency for Research on Carcer, Lyon.

Horakova, K., Sovcikova, A., Seemannova, Z., Syrova, D., Busanyova, K., Drobna, Z. and Ferencik, M. (2001) Detection of drug-induced, superoxide-mediated cell damage and its prevention by antioxidants. Free Radic Biol Med, 30, 650-664.

Hubinger, G., Schneider, C., Stohr, D., Ruff, H., Kirchner, D., Schwanen, C., Schmid, M., Bergmann, L. and Muller, E. (2004) CD30-induced up-regulation of the inhibitor of apoptosis genes cIAP1 and cIAP2 in anaplastic large cell lymphoma cells. Exp Hematol, 32, 382-389.

Hung, H.S., Wu, W.J., Cheng, Y.W., Wu, M.F., Chang, K.L. and Lee, H. (2005) Cooking oil fumes improve lung adenocarcinoma cell survival through c-IAP2 induction. J Toxicol Environ Health A, 68, 1525-1535.

Hussain, S.P., Amstad, P., Raja, K., Sawyer, M., Hofseth, L., Shields, P.G., Hewer, A., Phillips, D.H., Ryberg, D., Haugen, A. and Harris, C.C. (2001) Mutability of p53 hotspot codons to benzo(a)pyrene diol epoxide (BPDE) and the frequency of p53 mutations in nontumorous human lung. Cancer Res, 61, 6350-6355.

Hsu, C.W. (1999) Polycyclic aromatic hydrocarbons and particles in cooking smoke. Master thesis, Institute of Environmental Health, National Taiwan University.

Hunter, A.M., Kottachchi, D., Lewis, J., Duckett, C.S., Korneluk, R.G. and Liston, P. (2003) A novel ubiquitin fusion system bypasses the mitochondria and generates biologically active Smac/DIABLO. J Biol Chem, 278, 7494-7499.

Jamison, J.M., Gilloteaux, J., Taper, H.S. and Summers, J.L. (2001) Evaluation of the in vitro and in vivo antitumor activities of vitamin C and K-3 combinations against human prostate cancer. J Nutr, 131, 158S-160S.

Janmaat, M.L., Rodriguez, J.A., Gallegos-Ruiz, M., Kruyt, F.A. and Giaccone, G. (2006) Enhanced cytotoxicity induced by gefitinib and specific inhibitors of the Ras or phosphatidyl inositol-3 kinase pathways in non-small cell lung cancer cells. Int J Cancer, 118, 209-214.

Jeffrey, A.M., Jennette, K.W., Blobstein, S.H., Weinstein, I.B., Beland, F.A., Harvey, R.G., Kasal, H., Miura, I. and Nakanishi, K. (1976) Letter: Benzo[a]pyrene-nucleic acid derivative found in vivo: structure of a benzo[a]pyrenetetrahydrodiol epoxide-guanosine adduct. J Am Chem Soc, 98, 5714-5715.

Jeffrey, A.M., Weinstein, I.B., Jennette, K.W., Grzeskowiak, K., Nakanishi, K., Harvey, R.G., Autrup, H. and Harris, C. (1977) Structures of benzo(a)pyrene--nucleic acid adducts formed in human and bovine bronchial explants. Nature, 269, 348-350.

Jin, M., Inoue, S., Umemura, T., Moriya, J., Arakawa, M., Nagashima, K. and Kato, H. (2001) Cyclin D1, p16 and retinoblastoma gene product expression as a predictor for prognosis in non-small cell lung cancer at stages I and II. Lung Cancer, 34, 207-218.

Katsumata, N., Eguchi, K., Fukuda, M., Yamamoto, N., Ohe, Y., Oshita, F., Tamura, T., Shinkai, T. and Saijo, N. (1996) Serum levels of cytokines in patients with untreated primary lung cancer. Clin Cancer Res, 2, 553-559.

Kiechle, F.L. and Zhang, X. (2002) Apoptosis: biochemical aspects and clinical implications. Clin Chim Acta, 326, 27-45.

Kim, H.J., Kim, K.W., Yu, B.P. and Chung, H.Y. (2000) The effect of age on cyclooxygenase-2 gene expression: NF-kappaB activation and IkappaBalpha degradation. Free Radic Biol Med, 28, 683-692.

Ko, J.L., Cheng, Y.W., Chang, S.L., Su, J.M., Chen, C.Y. and Lee, H. (2000a) MDM2 mRNA expression is a favorable prognostic factor in non-small-cell lung cancer. Int J Cancer, 89, 265-270.

Ko, Y.C., Cheng, L.S., Lee, C.H., Huang, J.J., Huang, M.S., Kao, E.L., Wang, H.Z. and Lin, H.J. (2000b) Chinese food cooking and lung cancer in women nonsmokers. Am J Epidemiol, 151, 140-147.

Ko, Y.C., Lee, C.H., Chen, M.J., Huang, C.C., Chang, W.Y., Lin, H.J., Wang, H.Z. and Chang, P.Y. (1997) Risk factors for primary lung cancer among non-smoking women in Taiwan. Int J Epidemiol, 26, 24-31.

Kodani, M., Igishi, T., Matsumoto, S., Chikumi, H., Shigeoka, Y., Nakanishi, H., Morita, M., Yasuda, K., Hitsuda, Y. and Shimizu, E. (2005) Suppression of phosphatidylinositol 3-kinase/Akt signaling pathway is a determinant of the sensitivity to a novel histone deacetylase inhibitor, FK228, in lung adenocarcinoma cells. Oncol Rep, 13, 477-483.

Krajewska, M., Krajewski, S., Banares, S., Huang, X., Turner, B., Bubendorf, L., Kallioniemi, O.P., Shabaik, A., Vitiello, A., Peehl, D., Gao, G.J. and Reed, J.C. (2003) Elevated expression of inhibitor of apoptosis proteins in prostate cancer. Clin Cancer Res, 9, 4914-4925.

Krasilnikov, M.A. (2000) Phosphatidylinositol-3 kinase dependent pathways: the role in control of cell growth, survival, and malignant transformation. Biochemistry (Mosc), 65, 59-67.

Kreuz, S., Siegmund, D., Scheurich, P. and Wajant, H. (2001) NF-kappaB inducers upregulate cFLIP, a cycloheximide-sensitive inhibitor of death receptor signaling. Mol Cell Biol, 21, 3964-3973.

Krystal, G.W., Sulanke, G. and Litz, J. (2002) Inhibition of phosphatidylinositol 3-kinase-Akt signaling blocks growth, promotes apoptosis, and enhances sensitivity of small cell lung cancer cells to chemotherapy. Mol Cancer Ther, 1, 913-922.

LaCasse, E.C., Baird, S., Korneluk, R.G. and MacKenzie, A.E. (1998) The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene, 17, 3247-3259.

Lee, Y.C., Tang, Y.C., Chen, Y.H., Wong, C.M. and Tsou, A.P. (2003) Selenite-induced survival of HuH7 hepatoma cells involves activation of focal adhesion kinase-phosphatidylinositol 3-kinase-Akt pathway and Rac1. J Biol Chem, 278, 39615-39624.

Levkau, B., Garton, K.J., Ferri, N., Kloke, K., Nofer, J.R., Baba, H.A., Raines, E.W. and Breithardt, G. (2001) xIAP induces cell-cycle arrest and activates nuclear factor-kappaB : new survival pathways disabled by caspase-mediated cleavage during apoptosis of human endothelial cells. Circ Res, 88, 282-290.

Li, F., Ackermann, E.J., Bennett, C.F., Rothermel, A.L., Plescia, J., Tognin, S., Villa, A., Marchisio, P.C. and Altieri, D.C. (1999) Pleiotropic cell-division defects and apoptosis induced by interference with survivin function. Nat Cell Biol, 1, 461-466.

Li, S., Pan, D. and Wang, G. (1994) Analysis of polycyclic aromatic hydrocarbons in cooking oil fumes. Arch Environ Health, 49, 119-122.
Li, X.A., Bianchi, C. and Sellke, F.W. (2001) Rat aortic smooth muscle cell density affects activation of MAP kinase and Akt by menadione and PDGF homodimer BB. J Surg Res, 100, 197-204.

Lin, M.T., Lee, R.C., Yang, P.C., Ho, F.M. and Kuo, M.L. (2001) Cyclooxygenase-2 inducing Mcl-1-dependent survival mechanism in human lung adenocarcinoma CL1.0 cells. Involvement of phosphatidylinositol 3-kinase/Akt pathway. J Biol Chem, 276, 48997-49002.

Lin, S.Y., Tsai, S.J., Wang, L.H., Wu, M.F. and Lee, H. (2002) Protection by quercetin against cooking oil fumes-induced DNA damage in human lung adenocarcinoma CL-3 cells: role of COX-2. Nutr Cancer, 44, 95-101.

Liu, S.L., Lin, X., Shi, D.Y., Cheng, J., Wu, C.Q. and Zhang, Y.D. (2002) Reactive oxygen species stimulated human hepatoma cell proliferation via cross-talk between PI3-K/PKB and JNK signaling pathways. Arch Biochem Biophys, 406, 173-182.

Liu, Z.M., Chen, G.G., Ng, E.K., Leung, W.K., Sung, J.J. and Chung, S.C. (2004) Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human gastric cancer cells. Oncogene, 23, 503-513.

Lofroth, G., Stensman, C. and Brandhorst-Satzkorn, M. (1991) Indoor sources of mutagenic aerosol particulate matter: smoking, cooking and incense burning. Mutat Res, 261, 21-28.

Malins, D.C., Hellstrom, K.E., Anderson, K.M., Johnson, P.M. and Vinson, M.A. (2002) Antioxidant-induced changes in oxidized DNA. Proc Natl Acad Sci U S A, 99, 5937-5941.

Manchester, D.K., Weston, A., Choi, J.S., Trivers, G.E., Fennessey, P.V., Quintana, E., Farmer, P.B., Mann, D.L. and Harris, C.C. (1988) Detection of benzo[a]pyrene diol epoxide-DNA adducts in human placenta. Proc Natl Acad Sci U S A, 85, 9243-9247.


Martelli, A.M., Tazzari, P.L., Tabellini, G., Bortul, R., Billi, A.M., Manzoli, L., Ruggeri, A., Conte, R. and Cocco, L. (2003) A new selective AKT pharmacological inhibitor reduces resistance to chemotherapeutic drugs, TRAIL, all-trans-retinoic acid, and ionizing radiation of human leukemia cells. Leukemia, 17, 1794-1805.

Martin, D., Salinas, M., Fujita, N., Tsuruo, T. and Cuadrado, A. (2002) Ceramide and reactive oxygen species generated by H2O2 induce caspase-3-independent degradation of Akt/protein kinase B. J Biol Chem, 277, 42943-42952.

McCann, J., Choi, E., Yamasaki, E. and Ames, B.N. (1975) Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals. Proc Natl Acad Sci U S A, 72, 5135-5139.

McKeown, D.J., Brown, D.J., Kelly, A., Wallace, A.M. and McMillan, D.C. (2004) The relationship between circulating concentrations of C-reactive protein, inflammatory cytokines and cytokine receptors in patients with non-small-cell lung cancer. Br J Cancer, 91, 1993-1995.

Messmer, U.K., Pereda-Fernandez, C., Manderscheid, M. and Pfeilschifter, J. (2001) Dexamethasone inhibits TNF-alpha-induced apoptosis and IAP protein downregulation in MCF-7 cells. Br J Pharmacol, 133, 467-476.

Mone, A.P., Huang, P., Pelicano, H., Cheney, C.M., Green, J.M., Tso, J.Y., Johnson, A.J., Jefferson, S., Lin, T.S. and Byrd, J.C. (2004) Hu1D10 induces apoptosis concurrent with activation of the AKT survival pathway in human chronic lymphocytic leukemia cells. Blood, 103, 1846-1854.

Nakashio, A., Fujita, N., Rokudai, S., Sato, S. and Tsuruo, T. (2000) Prevention of phosphatidylinositol 3''-kinase-Akt survival signaling pathway during topotecan-induced apoptosis. Cancer Res, 60, 5303-5309.

Neri, L.M., Borgatti, P., Tazzari, P.L., Bortul, R., Cappellini, A., Tabellini, G., Bellacosa, A., Capitani, S. and Martelli, A.M. (2003) The phosphoinositide 3-kinase/AKT1 pathway involvement in drug and all-trans-retinoic acid resistance of leukemia cells. Mol Cancer Res, 1, 234-246.

Nguyen, D.M., Chen, G.A., Reddy, R., Tsai, W., Schrump, W.D., Cole, G., Jr. and Schrump, D.S. (2004) Potentiation of paclitaxel cytotoxicity in lung and esophageal cancer cells by pharmacologic inhibition of the phosphoinositide 3-kinase/protein kinase B (Akt)-mediated signaling pathway. J Thorac Cardiovasc Surg, 127, 365-375.

Nie, Z., Mei, Y., Ford, M., Rybak, L., Marcuzzi, A., Ren, H., Stiles, G.L. and Ramkumar, V. (1998) Oxidative stress increases A1 adenosine receptor expression by activating nuclear factor kappa B. Mol Pharmacol, 53, 663-669.

Nishihara, H., Hwang, M., Kizaka-Kondoh, S., Eckmann, L. and Insel, P.A. (2004) Cyclic AMP promotes cAMP-responsive element-binding protein-dependent induction of cellular inhibitor of apoptosis protein-2 and suppresses apoptosis of colon cancer cells through ERK1/2 and p38 MAPK. J Biol Chem, 279, 26176-26183.

Nutter, L.M., Cheng, A.L., Hung, H.L., Hsieh, R.K., Ngo, E.O. and Liu, T.W. (1991) Menadione: spectrum of anticancer activity and effects on nucleotide metabolism in human neoplastic cell lines. Biochem Pharmacol, 41, 1283-1292.

Okouoyo, S., Herzer, K., Ucur, E., Mattern, J., Krammer, P.H., Debatin, K.M. and Herr, I. (2004) Rescue of death receptor and mitochondrial apoptosis signaling in resistant human NSCLC in vivo. Int J Cancer, 108, 580-587.

Pahl, H.L. (1999) Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene, 18, 6853-6866.

Parejo, I., Codina, C., Petrakis, C. and Kefalas, P. (2000) Evaluation of scavenging activity assessed by Co(II)/EDTA-induced luminol chemiluminescence and DPPH* (2,2-diphenyl-1-picrylhydrazyl) free radical assay. J Pharmacol Toxicol Methods, 44, 507-512.

Phillips, D.H., Hewer, A., Martin, C.N., Garner, R.C. and King, M.M. (1988) Correlation of DNA adduct levels in human lung with cigarette smoking. Nature, 336, 790-792.

Phillips, D.H., Hewer, A., Malcolm, A.D., Ward, P. and Coleman, D.V. (1990) Smoking and DNA damage in cervical cells. Lancet, 335, 417.

Pryhuber, G.S., Huyck, H.L., Staversky, R.J., Finkelstein, J.N. and O''Reilly, M.A. (2000) Tumor necrosis factor-alpha-induced lung cell expression of antiapoptotic genes TRAF1 and cIAP2. Am J Respir Cell Mol Biol, 22, 150-156.

Qu, Y.H., Xu, G.X., Zhou, J.Z., Chen, T.D., Zhu, L.F., Shields, P.G., Wang, H.W. and Gao, Y.T. (1992) Genotoxicity of heated cooking oil vapors. Mutat Res, 298, 105-111.

Renard, P., Percherancier, Y., Kroll, M., Thomas, D., Virelizier, J.L., Arenzana-Seisdedos, F. and Bachelerie, F. (2000) Inducible NF-kappaB activation is permitted by simultaneous degradation of nuclear IkappaBalpha. J Biol Chem, 275, 15193-15199.

Rohayem, J., Diestelkoetter, P., Weigle, B., Oehmichen, A., Schmitz, M., Mehlhorn, J., Conrad, K. and Rieber, E.P. (2000) Antibody response to the tumor-associated inhibitor of apoptosis protein survivin in cancer patients. Cancer Res, 60, 1815-1817.

Roman, J., Gimenez, A., Lluis, J.M., Gasso, M., Rubio, M., Caballeria, J., Pares, A., Rodes, J. and Fernandez-Checa, J.C. (2000) Enhanced DNA binding and activation of transcription factors NF-kappa B and AP-1 by acetaldehyde in HEPG2 cells. J Biol Chem, 275, 14684-14690.

Rothe, M., Pan, M.G., Henzel, W.J., Ayres, T.M. and Goeddel, D.V. (1995) The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell, 83, 1243-1252.

Roy, N., Mahadevan, M.S., McLean, M., Shutler, G., Yaraghi, Z., Farahani, R., Baird, S., Besner-Johnston, A., Lefebvre, C., Kang, X. and et al. (1995) The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell, 80, 167-178.

Roy, N., Deveraux, Q.L., Takahashi, R., Salvesen, G.S. and Reed, J.C. (1997) The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. Embo J, 16, 6914-6925.

Schimmer, A.D. (2004) Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice. Cancer Res, 64, 7183-7190.

Schoemaker, M.H., Ros, J.E., Homan, M., Trautwein, C., Liston, P., Poelstra, K., van Goor, H., Jansen, P.L. and Moshage, H. (2002) Cytokine regulation of pro- and anti-apoptotic genes in rat hepatocytes: NF-kappaB-regulated inhibitor of apoptosis protein 2 (cIAP2) prevents apoptosis. J Hepatol, 36, 742-750.

Schoket, B., Horkay, I., Kosa, A., Paldeak, L., Hewer, A., Grover, P.L. and Phillips, D.H. (1990) Formation of DNA adducts in the skin of psoriasis patients, in human skin in organ culture, and in mouse skin and lung following topical application of coal-tar and juniper tar. J Invest Dermatol, 94, 241-246.

Seidman, L.A., Moore, C.J. and Gould, M.N. (1988) 32P-postlabeling analysis of DNA adducts in human and rat mammary epithelial cells. Carcinogenesis, 9, 1071-1077.

Shiozaki, E.N. and Shi, Y. (2004) Caspases, IAPs and Smac/DIABLO: mechanisms from structural biology. Trends Biochem Sci, 29, 486-494.

Singhal, S., Vachani, A., Antin-Ozerkis, D., Kaiser, L.R. and Albelda, S.M. (2005) Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review. Clin Cancer Res, 11, 3974-3986.

Sithanandam, G., Smith, G.T., Fields, J.R., Fornwald, L.W. and Anderson, L.M. (2005) Alternate paths from epidermal growth factor receptor to Akt in malignant versus nontransformed lung epithelial cells: ErbB3 versus Gab1. Am J Respir Cell Mol Biol, 33, 490-499.

Sonoda, Y., Matsumoto, Y., Funakoshi, M., Yamamoto, D., Hanks, S.K. and Kasahara, T. (2000) Anti-apoptotic role of focal adhesion kinase (FAK). Induction of inhibitor-of-apoptosis proteins and apoptosis suppression by the overexpression of FAK in a human leukemic cell line, HL-60. J Biol Chem, 275, 16309-16315.

Suliman, H.B., Carraway, M.S., Welty-Wolf, K.E., Whorton, A.R. and Piantadosi, C.A. (2003) Lipopolysaccharide stimulates mitochondrial biogenesis via activation of nuclear respiratory factor-1. J Biol Chem, 278, 41510-41518.

Swinney, D.C., Xu, Y.Z., Scarafia, L.E., Lee, I., Mak, A.Y., Gan, Q.F., Ramesha, C.S., Mulkins, M.A., Dunn, J., So, O.Y., Biegel, T., Dinh, M., Volkel, P., Barnett, J., Dalrymple, S.A., Lee, S. and Huber, M. (2002) A small molecule ubiquitination inhibitor blocks NF-kappa B-dependent cytokine expression in cells and rats. J Biol Chem, 277, 23573-23581.

Ueda, T., Akiyama, N., Sai, H., Oya, N., Noda, M., Hiraoka, M. and Kizaka-Kondoh, S. (2001) c-IAP2 is induced by ionizing radiation through NF-kappaB binding sites. FEBS Lett, 491, 40-44.

Uzzo, R.G., Leavis, P., Hatch, W., Gabai, V.L., Dulin, N., Zvartau, N. and Kolenko, V.M. (2002) Zinc inhibits nuclear factor-kappa B activation and sensitizes prostate cancer cells to cytotoxic agents. Clin Cancer Res, 8, 3579-3583.

Vivanco, I. and Sawyers, C.L. (2002) The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer, 2, 489-501.

Wang, C.Y., Mayo, M.W., Korneluk, R.G., Goeddel, D.V. and Baldwin, A.S., Jr. (1998a) NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science, 281, 1680-1683.

Wang, Q., Wang, X. and Evers, B.M. (2003) Induction of cIAP-2 in human colon cancer cells through PKC delta/NF-kappa B. J Biol Chem, 278, 51091-51099.

Wang, Y.C., Chen, C.Y., Chen, S.K., Cherng, S.H., Ho, W.L. and Lee, H. (1998b) High frequency of deletion mutations in p53 gene from squamous cell lung cancer patients in Taiwan. Cancer Res, 58, 328-333.

Woo, J.H., Kim, Y.H., Choi, Y.J., Kim, D.G., Lee, K.S., Bae, J.H., Min do, S., Chang, J.S., Jeong, Y.J., Lee, Y.H., Park, J.W. and Kwon, T.K. (2003) Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release of cytochrome c and inhibition of Akt. Carcinogenesis, 24, 1199-1208.

Woo, K.J., Jeong, Y.J., Park, J.W. and Kwon, T.K. (2004) Chrysin-induced apoptosis is mediated through caspase activation and Akt inactivation in U937 leukemia cells. Biochem Biophys Res Commun, 325, 1215-1222.

Wu-Williams, A.H., Dai, X.D., Blot, W., Xu, Z.Y., Sun, X.W., Xiao, H.P., Stone, B.J., Yu, S.F., Feng, Y.P., Ershow, A.G. and et al. (1990) Lung cancer among women in north-east China. Br J Cancer, 62, 982-987.

Wu, P.F., Chiang, T.A., Wang, L.F., Chang, C.S. and Ko, Y.C. (1998) Nitro-polycyclic aromatic hydrocarbon contents of fumes from heated cooking oils and prevention of mutagenicity by catechin. Mutat Res, 403, 29-34.

Xie, H., Zhao, Z. and Wang, S. (1998) [PAH-DNA adduct in human lung cancer explants. A preliminary study]. Zhonghua Zhong Liu Za Zhi, 20, 187-190.

Xie, S., Lin, H.K., Ni, J., Yang, L., Wang, L., di Sant''Agnese, P.A. and Chang, C. (2004) Regulation of interleukin-6-mediated PI3K activation and neuroendocrine differentiation by androgen signaling in prostate cancer LNCaP cells. Prostate, 60, 61-67.

Xiong, A., Clarke-Katzenberg, R.H., Valenzuela, G., Izumi, K.M. and Millan, M.T. (2004) Epstein-Barr virus latent membrane protein 1 activates nuclear factor-kappa B in human endothelial cells and inhibits apoptosis. Transplantation, 78, 41-49.

Yamamoto, Y. and Gaynor, R.B. (2004) IkappaB kinases: key regulators of the NF-kappaB pathway. Trends Biochem Sci, 29, 72-79.

Yan, Z., Subbaramaiah, K., Camilli, T., Zhang, F., Tanabe, T., McCaffrey, T.A., Dannenberg, A.J. and Weksler, B.B. (2000) Benzo[a]pyrene induces the transcription of cyclooxygenase-2 in vascular smooth muscle cells. Evidence for the involvement of extracellular signal-regulated kinase and NF-kappaB. J Biol Chem, 275, 4949-4955.

Yanagawa, H., Sone, S., Takahashi, Y., Haku, T., Yano, S., Shinohara, T. and Ogura, T. (1995) Serum levels of interleukin 6 in patients with lung cancer. Br J Cancer, 71, 1095-1098.

Yang, L., Mashima, T., Sato, S., Mochizuki, M., Sakamoto, H., Yamori, T., Oh-Hara, T. and Tsuruo, T. (2003) Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic effect of a novel polyarginine-conjugated Smac peptide. Cancer Res, 63, 831-837.

Yang, S.C., Jenq, S.N., Kang, Z.C. and Lee, H. (2000) Identification of benzo[a]pyrene 7,8-diol 9,10-epoxide N2-deoxyguanosine in human lung adenocarcinoma cells exposed to cooking oil fumes from frying fish under domestic conditions. Chem Res Toxicol, 13, 1046-1050.

Zhang, X., Rosenstein, B.S., Wang, Y., Lebwohl, M. and Wei, H. (1997) Identification of possible reactive oxygen species involved in ultraviolet radiation-induced oxidative DNA damage. Free Radic Biol Med, 23, 980-985.

Zhang, Z., Gao, N., He, H., Huang, C., Luo, J. and Shi, X. (2004) Vanadate activated Akt and promoted S phase entry. Mol Cell Biochem, 255, 227-237.

Zhong, L., Goldberg, M.S., Parent, M.E. and Hanley, J.A. (1999) Risk of developing lung cancer in relation to exposure to fumes from Chinese-style cooking. Scand J Work Environ Health, 25, 309-316.

Zou, T., Rao, J.N., Guo, X., Liu, L., Zhang, H.M., Strauch, E.D., Bass, B.L. and Wang, J.Y. (2004) NF-kappaB-mediated IAP expression induces resistance of intestinal epithial cells to apoptosis after polyamine depletion. Am J Physiol Cell Physio, 286, C1009-1018.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top