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研究生:陳碩爵
研究生(外文):Shuo-Chueh Chen
論文名稱:C型血管內皮成長因子在第一期非小細胞肺癌術後預後因子之角色以及抑制肺癌細胞移動之新藥開發
論文名稱(外文):Role of Vascular Endothelial Growth Factor C in Resected Stage I of Non-small Cell Lung Cancer and New Drugs Investigation for Anti-migration of Lung Cancer Cell
指導教授:吳介信吳介信引用關係陳志毅陳志毅引用關係
學位類別:博士
校院名稱:中國醫藥大學
系所名稱:臨床醫學研究所博士班
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:2014
畢業學年度:102
語文別:英文
論文頁數:52
中文關鍵詞:肺癌C型血管內皮成長因子新藥開發
外文關鍵詞:lung cancervascular endothelial growth factor Cnew drugs investigation
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Early stage of Non-small-cell lung cancer (NSCLC) can be treated by surgical resection and had relative better prognosis. But only 20% was stage I disease, and early recurrence may influence the prognosis. When NSCLC makes progress to late stage, the high metastatic ability leads to high mortality rate. Our study focused on the role of VEGF-C in predicting early recurrence of stage I resected NSCLC patients and investigate new compound, dihydroaustrasulfone alcohol, from murine soft coral and its mechanism in inhibition of cancer cell migration.
In chapter 1, we hypothesize that vascular endothelial growth factor C (VEGF-C) plays a key role in predicting early recurrence and poor survival of patients with stage I NSCLC because VEGF-C induce lymphaniogenesis, which mediates tumor cell dissemination and the formation of lymph node metastases. The expression of VEGF-C was immuno-histochemically (IHC) analyzed in tumor samples of primary stage I NSCLC and correlated to early recurrence (< 36 months), disease free survival, and overall survival in all 49 patients. Early recurrence was identified in 16 patients (33%), and the early recurrent rate in strong and weak VEGF-C activity was significantly different (p=0.016). VEGF-C was also an independent risk factor in predicting early recurrence (HR=3.98, p=0.02). Patients with strong VEGF-C staining also had poor 3-year disease-free survival (46% vs. 84%, p=0.008) and overall survival (38% vs. 80%, p=0.007). We concluded that strong VEGF-C IHC staining may be a biomarker for predicting early recurrence and poor prognosis of resected stage I NSCLC. There should be more aggressive adjuvant therapy in this group of patients.
In chapter 2, we investigate a new natural marine substrate, Dihydroaustrasulfone alcohol, from soft coral against NSCLC cell line migration and tumor growth in Lewis lung cancer (LLC)-bearing mice and its regulation mechanism. Dihydroaustrasulfone alcohol, which was isolated from marine coral, has shown its antioxidant activity, but has not been reported to have an anti-cancer effect. We first discovered that dihydroaustrasulfone alcohol provided a concentration-dependent inhibitory effect on the migration and motility of human non-small cell lung carcinoma (NSCLC) A549 cells by trans-well and wound healing assays. The results of a zymography assay and Western blot showed that dihydroaustrasulfone alcohol suppressed the activities and protein expression of matrix metalloproteinase (MMP)-2 and MMP-9. Further investigation revealed that dihydroaustrasulfone alcohol suppressed the phosphorylation of ERK1/2, p38, and JNK1/2. Dihydroaustrasulfone alcohol also suppressed the expression of PI3K and the phosphorylation of Akt. Furthermore, dihydroaustrasulfone alcohol markedly inhibited tumor growth in Lewis lung cancer (LLC)-bearing mice. We concluded that dihydroaustrasulfone alcohol is a new pure compound with anti-migration and anti-tumor growth activity in lung cancer and might be applied to clinical treatment in the future.


Contents
Abstract ....................................................................................................1

Brief Introduction
1. Background ...........................................................................................3
2. References .............................................................................................4


Chapter 1
Vascular Endothelial Growth Factor C as a Predictor of Early Recurrence and Poor Prognosis of Resected Stage I Non-small Cell Lung Cancer .....7

1.Introduction ............................................................................................8
2. Materials and Methods...........................................................................9
3. Results .............................................................................................. ..12
4. Discussion............................................................................................13
5. Reference ............................................................................................15
6. Tables and Figures………...................................................................18

Chapter 2

Inhibitory effect of Dihydroaustrasulfone alcohol on the migration of human non-small cell lung carcinoma A549 cells and the antitumor effect on a Lewis lung carcinoma-bearing tumor model in C57BL/6J mice....24

1. Introduction.........................................................................................25
2. Results and Discussion (including figures).........................................27
3. Experimental Section...........................................................................38
4. References and Notes...........................................................................46

Conclusions.............................................................................................52


(1) Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997;111:1710-7.
(2) Goodgame B, Viswanathan A, Miller CR, Gao F, Meyers B, Battafarano RJ, et al. A clinical model to estimate recurrence risk in resected stage I non-small cell lung cancer. Am J Clin Oncol 2008;31:22-8.
(3) Brock MV, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S, et al. DNA Methylation Markers and Early Recurrence in Stage I Lung Cancer. N Engl J Med 2008;358:1118-28.
(4) Lee HJ, Jo J, Son DS, Lee J, Choi YS, Kim K, et al. Predicting recurrence using the clinical factors of patients with non-small cell lung cancer after curative resection. J Korean Med Sci 2009;24:824-30.
(5) Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, et al. Vinorelbine plus cisplatin vs.observation in resected non-small-cell lung cancer. N Engl J Med 2005;352:2589 –97.
(6) Strauss GMH, Maddaus JE, Johnstone MA. Adjuvant chemotherapy
in Stage IB non-small cell lung cancer (NSCLC): update of Cancer
and Leukemia Group B (CALGB) protocol 9633. J Clin Oncol. 2006;24(suppl):7007.
(7) Mandriota SJ, Jussila L, Jeltsch M, Compagni A, Baetens D, Prevo R, et al. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J 2001;20:672-82.

(8) Man, S.; Gao, W.; Zhang, Y.; Liu, Z.; Yan, L.; Huang, L.; Liu, C., Formosanin C-inhibited pulmonary metastasis through repression of matrix metalloproteinases on mouse lung adenocarcinoma. Cancer Biol. Ther. 2011, 11, (6), 592-8.
(9) Lirdprapamongkol, K.; Kramb, J. P.; Suthiphongchai, T.; Surarit, R.; Srisomsap, C.; Dannhardt, G.; Svasti, J., Vanillin suppresses metastatic potential of human cancer cells through PI3K inhibition and decreases angiogenesis in vivo. J. Agric. Food Chem. 2009, 57, (8), 3055-63.
(10) Kodate, M.; Kasai, T.; Hashimoto, H.; Yasumoto, K.; Iwata, Y.; Manabe, H., Expression of matrix metalloproteinase (gelatinase) in T1 adenocarcinoma of the lung. Pathol. Int. 1997, 47, (7), 461-9.
(11) Weng, C. J.; Wu, C. F.; Huang, H. W.; Wu, C. H.; Ho, C. T.; Yen, G. C., Evaluation of anti-invasion effect of resveratrol and related methoxy analogues on human hepatocarcinoma cells. J. Agric. Food Chem. 2010, 58, (5), 2886-94.
(12) Campbell, I. G.; Russell, S. E.; Choong, D. Y.; Montgomery, K. G.; Ciavarella, M. L.; Hooi, C. S.; Cristiano, B. E.; Pearson, R. B.; Phillips, W. A., Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res. 2004, 64, (21), 7678-81.
(13) Gupta, A. K.; Soto, D. E.; Feldman, M. D.; Goldsmith, J. D.; Mick, R.; Hahn, S. M.; Machtay, M.; Muschel, R. J.; McKenna, W. G., Signaling pathways in NSCLC as a predictor of outcome and response to therapy. Lung 2004, 182, (3), 151-62.
(14) Shih, Y. W.; Chen, P. S.; Wu, C. H.; Jeng, Y. F.; Wang, C. J., Alpha-chaconine-reduced metastasis involves a PI3K/Akt signaling pathway with downregulation of NF-kappaB in human lung adenocarcinoma A549 cells. J. Agric. Food Chem. 2007, 55, (26), 11035-43.
(15) Tseng, Y. J.; Wen, Z. H.; Dai, C. F.; Chiang, M. Y.; Sheu, J. H., Nanolobatolide, a new C18 metabolite from the Formosan soft coral Sinularia nanolobata. Org. Lett. 2009, 11, (21), 5030-2.
(16) Chao, C. H.; Wen, Z. H.; Wu, Y. C.; Yeh, H. C.; Sheu, J. H., Cytotoxic and anti-inflammatory cembranoids from the soft coral Lobophytum crassum. J. Nat. Prod. 2008, 71, (11), 1819-24.
(17) Mantovani, A.; Allavena, P.; Sica, A.; Balkwill, F., Cancer-related inflammation. Nature 2008, 454, (7203), 436-44.


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