進階搜尋


   電子論文尚未授權公開,紙本請查館藏目錄
(※如查詢不到或館藏狀況顯示「閉架不公開」,表示該本論文不在書庫,無法取用。)
系統識別號 U0026-2508202019034900
論文名稱(中文) 血漿型凝溶膠蛋白作為口腔癌生物標記物及其功能性角色
論文名稱(英文) Plasma gelsolin as a biomarker of head and neck cancer and its functional roles
校院名稱 成功大學
系所名稱(中) 基礎醫學研究所
系所名稱(英) Institute of Basic Medical Sciences
學年度 108
學期 2
出版年 109
研究生(中文) 邱貞慈
研究生(英文) Chen-Tzu Chiu
學號 S58001284
學位類別 博士
語文別 英文
論文頁數 82頁
口試委員 指導教授-謝達斌
口試委員-張國威
口試委員-劉柯俊
口試委員-王憶卿
口試委員-陳玉玲
召集委員-蔡曜聲
中文關鍵字 血漿凝溶膠蛋白  細胞質凝溶膠蛋白  頭頸癌  細胞移動能力 
英文關鍵字 plasma gelsolin  cytosolic gelsolin  head and neck cancer  cell motility 
學科別分類
中文摘要 凝溶膠蛋白是一種多功能肌動蛋白結合蛋白,可調節細胞結構,運動性和凋亡。 凝溶膠蛋白的兩種最豐富和最著名的亞型是血漿凝溶膠蛋白和胞質凝溶膠蛋白,血漿凝溶膠蛋白與胞質凝溶膠蛋白的區別在於其分泌出細胞後N端氨基端肽仍保留在成熟蛋白中。據研究指出,胞質凝溶膠蛋白可以預測頭頸癌和其他惡性腫瘤的疾病進展,而循環中的血漿凝溶膠蛋白濃度則與感染與發炎疾病的預後密切相關。近年來,我們發現胞質凝溶膠蛋白通過常見的分子信號傳遞來調控頭頸癌的耐藥性。然而,血漿凝溶膠蛋白在癌症進展和預後中的潛在能力仍有待研究。在這項研究中,證實了在具有更高的轉移能力SCC25細胞培養基中與HONE-1細胞相比有更高血漿凝溶膠蛋白的表現。此外,我們的結果表明,透過整合蛋白(integrin)依賴性吞噬作用,經外源血漿凝溶膠蛋白誘導後,細胞內凝溶膠蛋白表現隨著外源型血漿凝溶膠蛋白濃度增加而增加。此外,內生性血漿凝溶膠蛋白的過度表達或剃除證明了血漿凝溶膠蛋白在上皮-間質轉化和遷移以及細胞侵襲中的正向作用。這些結果表明,血漿凝溶膠蛋白在頭頸癌中具有調節腫瘤活性的作用。除此之外,頭頸癌盤據台灣前十大死因排名之中,當疾病越晚期被診斷,存活率也會隨之降低。儘管晚期診斷是導致頭頸癌死亡的主要因素,但目前尚無令人滿意的生物標記物可用於早期頭頸癌檢測。血漿凝溶膠蛋白是人體循環系統中最豐富的蛋白質之一,也是發炎反應的指標,或許可做為頭頸癌的生物標記物和患者臨床預後指標。經由比對202名頭頸癌患者和45名健康對照後,我們證明頭頸癌患者血液中的血漿凝溶膠蛋白濃度顯著低於健康對照組。此外,血液中的血漿凝溶膠蛋白做為頭頸癌的獨立診斷生物標誌物,在檢測靈敏性 (82.7%)和特異性(95.6%)均優於其他候選生物標記物。同時,血漿凝溶膠蛋白和sFasL的結合,更可在早期疾病檢測中達到更高的偵測靈敏度(90.6%)。此外,血中較高的血漿凝溶膠蛋白可預測5年後較高的總生存率和無疾病進展生存率。因此,血漿凝溶膠蛋白不僅在癌症的遷移和侵襲中扮演角色,還可以獨立作為臨床預後預測因子,同時結合sFasL 可在早期頭頸癌作為新型生物標記物。
英文摘要 Gelsolin (GSN) is a multifunctional actin-binding protein that acts as a regulator of cell structure, motility and apoptosis. The two most abundant and well-known isoforms of GSN are plasma and cytosolic GSN (cGSN), plasma gelsolin (pGSN) differs from cGSN by an extended amino-terminal peptide which remains in mature protein after secretion. It has been reported that cGSN could predict disease progression in head and neck cancer (HNC) and other malignancies, while circulating pGSN levels significantly correlate with the prognosis of infectious and inflammatory diseases. In recent years, we discovered that cGSN modulates drug resistance in HNC through a common molecular signaling regulation. However, the potential roles of pGSN in cancer progression and prognosis remain elusive. In this study, the higher expression of pGSN in the medium of SCC25 was confirmed, which has a higher metastatic ability compared to HONE-1 cells. Our results showed that intracellular GSN protein levels were augmented in a dose-dependent manner upon exogenous pGSN-induction through integrin-dependent endocytosis. Furthermore, overexpression or knockdown of endogenous pGSN demonstrated the confident role of pGSN in epithelial-mesenchymal transition and migration as well as invasion of cells. These results suggested the role of pGSN in HNC to act as a tumor activity modulator. Besides, HNC ranks top ten causes of death in Taiwan, and the mortality increases considerably when the disease is diagnosed in its late stages. Despite late diagnosis being a major factor contributing to HNC mortality, no satisfactory biomarkers exist for early disease detection. As one of the most abundant proteins in circulatory system and testified indicator of inflammation modulator, the pGSN may serve as a biomarker for HNC and as the predictor of patients’ clinical outcome. After screening 202 patients with HNC and 45 healthy controls, we demonstrated that circulating pGSN levels were significantly lower in patients with HNC than in healthy controls. Moreover, circulating pGSN outperformed other candidate biomarkers as an independent diagnostic biomarker of HNC in both sensitivity (82.7%) and specificity (95.6%). Receiver operating characteristic curves indicated that combined pGSN and sFasL levels further augmented this sensitivity (90.6%) for early disease detection. Moreover, higher pGSN levels predicted improved prognosis at both 5-year overall survival and progression-free survival. We conclude that pGSN not only plays a role in cancer migration and invasion, but also could be an independent predictor of favorable clinical outcomes and a novel biomarker for the early HNC detection in combination with sFasL.
論文目次 中文摘要 I
Abstract III
誌謝 V
Table of Contents VI
List of Tables IX
List of Figures X
Introduction 1
1-1 The socioeconomic impact of head and neck cancer in Taiwan 2
1-2 Structure of gelsolin and its relation with actin dynamic regulation 2
1-3 Biological functions of gelsolins 3
1-4 Gelsolin and cancers 4
1-5 Prognostic Value of pGSN in multiple clinical conditions 6
Motivation and Rationale 7
Significance 7
Materials and Methods 9
2-1 Reagents 10
2-2 HNC cell culture 10
2-3 Transfection of pGSN plasmid DNA or siRNA 10
2-4 RNA Interference and establishment of stable clone 11
2-5 Isolation of RNA and Quantitative Real-Time RT-PCR 11
2-6 Internalization of pGSN in HONE-1 cells 12
2-7 Fluorescence conjugated with pGSN recombinant protein 12
2-8 Cellular uptake and confocal laser scanning microscopy analysis 13
2-9 Immunogold Labelling 13
2-10 Transwell assay 13
2-11 Preparation of concentrated culture medium 14
2-12 Western blot analysis 14
2-13 Ethics statement 15
2-14 Clinicopathological characteristics and collection of plasma samples 15
2-15 Immunohistochemical grading of pGSN expression 16
2-16 Circulating pGSN and SCC-Ag detection from patient’ plasma using sandwich ELISA 16
2-17 Circulating biomarker detection 17
2-18 Data analysis 18
Results 20
3-1 SCC25 presented higher pGSN expression than HONE-1 cells 21
3-2 Exogenous pGSN upregulated intracellular GSN protein levels but not mRNA levels …………………………………………………………………………….21
3-3 Exogenous pGSN augmented intracellular GSN was demonstrated by GSN knockdown stable clones 21
3-4 Exogenous pGSN entered HONE-1 cells which upregulated intracellular GSN through integrin signaling 22
3-5 Cellular uptake of exogenous pGSN into HONE-1 cells 22
3-6 Exogenous pGSN increased the motility of HONE-1 cells in vitro 23
3-7 Modulating pGSN expression confer carcinogenic phenotypes in HONE-1 cells………………………………………………… ……………… ………….23
3-8 Overexpression of pGSN correlated with the promotion of migration and invasion in HONE-1 cells 23
3-9 Knockdown of pGSN in SCC25 decreased EMT and migration as well as invasion 24
3-10 Patient characteristics 24
3-11 Expression levels of pGSN in HNC patients 25
3-12 Diagnostic value of circulating pGSN in patients with HNC 25
3-13 pGSN as a valuable diagnostic tool for early HNC stage 26
3-14 Survival analysis of circulating pGSN in validation datasets 27
3-15 Prognostic impact of circulating pGSN and its relationship with other clinicopathological parameters 28
Discussion 29
Conclusion 38
References 40
Tables 53
Figures 57
Curriculum Vitae 81
參考文獻 Abedini, M. R., P. W. Wang, Y. F. Huang, M. Cao, C. Y. Chou, D. B. Shieh and B. K. Tsang (2014). "Cell fate regulation by gelsolin in human gynecologic cancers." Proc Natl Acad Sci USA. 111(40): 14442-14447.
Ankenbauer, T., J. A. Kleinschmidt, J. Vandekerckhove and W. W. Franke (1988). "Proteins regulating actin assembly in oogenesis and early embryogenesis of xenopus-xaevis - gelsolin is the major cytoplasmic actin-binding protein." J Cell Biol. 107(4): 1489-1498.
Argun, M., A. Baykan, F. Narin, A. Ozyurt, O. Pamukcu, F. Elmali, K. Uzum and N. Narin (2015). "Plasma gelsolin as a biomarker of acute rheumatic carditis." Cardiol Young. 25(7): 1276-1280.
Asare-Werehene, M., L. Communal, E. Carmona, T. Le, D. Provencher, A. M. Mes-Masson and B. K. Tsang (2019). "Pre-operative circulating plasma gelsolin predicts residual disease and detects early stage ovarian cancer." Sci Rep. 9(1): 13924.
Asare-Werehene, M., K. Nakka, A. Reunov, C. T. Chiu, W. T. Lee, M. R. Abedini, P. W. Wang, D. B. Shieh, F. J. Dilworth, E. Carmona, T. Le, A. M. Mes-Masson, D. Burger and B. K. Tsang (2020). "The exosome-mediated autocrine and paracrine actions of plasma gelsolin in ovarian cancer chemoresistance." Oncogene. 39(7): 1600-1616.
Barak, V., A. Meirovitz, V. Leibovici, J. Rachmut, T. Peretz, R. Eliashar and M. Gross (2015). "The diagnostic and prognostic value of tumor markers (CEA, SCC, CYFRA 21-1, TPS) in head and neck cancer patients." Anticancer Res. 35(10): 5519-5524.
Bermejo-Pareja, F., D. Antequera, T. Vargas, J. A. Molina and E. Carro (2010). "Saliva levels of Abeta1-42 as potential biomarker of Alzheimer's disease: a pilot study." BMC Neurol. 10(1).
Bohgaki, M., M. Matsumoto, T. Atsumi, T. Kondo, S. Yasuda, T. Horita, K. I. Nakayama, F. Okumura, S. Hatakeyama and T. Koike (2011). "Plasma gelsolin facilitates interaction between β2 glycoprotein I and α5β1 integrin." J Cell Mol Med. 15(1): 141-151.
Bonomi, M., A. Patsias, M. Posner and A. Sikora (2014). "The role of inflammation in head and neck cancer." Adv Exp Med Biol. 816: 107-127.
Boroumand-Noughabi, S., H. R. Sima, K. Ghaffarzadehgan, M. Jafarzadeh, H. R. Raziee, H. Hosseinnezhad, O. Moaven, M. T. Rajabi-Mashhadi, A. A. Azarian, M. Mashhadinejad and J. Tavakkol-Afshari (2010). "Soluble Fas might serve as a diagnostic tool for gastric adenocarcinoma." BMC Cancer. 10(1).
Bucki, R. and J. J. Pastore (2006). "Bacterial endotoxin as inhibitor of the enzymatic activity of human thrombin." Eur J Haematol. 76(6): 510-515.
Burtnick, L. D., E. K. Koepf, J. Grimes, E. Y. Jones, D. I. Stuart, P. J. McLaughlin and R. C. Robinson (1997). "The crystal structure of plasma gelsolin: implications for actin severing, capping, and nucleation." Cell. 90(4): 661-670.
Chen, C. C., S. H. Chiou, C. L. Yang, K. C. Chow, T. Y. Lin, H. W. Chang, W. C. You, H. W. Huang, C. M. Chen, N. C. Chen, F. P. Chou and M. C. Chou (2017). "Secreted gelsolin desensitizes and induces apoptosis of infiltrated lymphocytes in prostate cancer." Oncotarget. 8(44): 77152-77167.
Chen, Z., K. Li, X. Yin, H. Li, Y. Li, Q. Zhang, H. Wang and Y. Qiu (2019). "Lower expression of gelsolin in colon cancer and its diagnostic value in colon cancer patients." J Cancer. 10(5): 1288-1296.
Chhabra, D., N. J. Nosworthy and C. G. dos Remedios (2005). "The N-terminal fragment of gelsolin inhibits the interaction of DNase I with isolated actin, but not with the cofilin-actin complex." Proteomics. 5(12): 3131-3136.
Chiang, C. J., W. C. Lo, Y. W. Yang, S. L. You, C. J. Chen and M. S. Lai (2016). "Incidence and survival of adult cancer patients in Taiwan, 2002-2012." J Formos Med Assoc. 115(12): 1076-1088.
Chou, S. H. Y., P. S. Lee, R. G. Konigsberg, D. Gallacci, T. Chiou, K. Arai, S. Simmons, D. Bauer, S. K. Feske, E. H. Lo and M. M. Ning (2011). "Plasma-type gelsolin is decreased in human blood and cerebrospinal fluid after subarachnoid hemorrhage." Stroke. 42(12): 3624-3627.
Coussens, L. M. and Z. Werb (2002). "Inflammation and cancer." Nature. 420(6917): 860-867.
Dahl, B., F. V. Schiodt, P. Ott, R. Gvozdenovic, H. L. Yin and W. M. Lee (1999). "Plasma gelsolin is reduced in trauma patients." Shock. 12(2): 102-104.
Deng, R., J. Hao, W. Han, Y. Ni, X. Huang and Q. Hu (2015). "Gelsolin regulates proliferation, apoptosis, migration and invasion in human oral carcinoma cells." Oncol Lett. 9(5): 2129-2134.
DiNubile, M. J., T. P. Stossel, O. C. Ljunghusen, J. L. Ferrara and J. H. Antin (2002). "Prognostic implications of declining plasma gelsolin levels after allogeneic stem cell transplantation." Blood. 100(13): 4367-4371.
Dong, Y., H. L. Asch, A. Ying and B. B. Asch (2002). "Molecular mechanism of transcriptional repression of gelsolin in human breast cancer cells." Exp Cell Res. 276(2): 328-336.
Epstein, F. H., W. M. Lee and R. M. Galbraith (1992). "The Extracellular Actin-Scavenger System and Actin Toxicity." N Engl J Med. 326(20): 1335-1341.
Erukhimov, J. A., Z. L. Tang, B. A. Johnson, M. P. Donahoe, J. A. Razzack, K. F. Gibson, W. M. Lee, K. J. Wasserloos, S. A. Watkins and B. R. Pitt (2000). "Actin-containing sera from patients with adult respiratory distress syndrome are toxic to sheep pulmonary endothelial cells." Am J Respir Crit Care Med. 162(1): 288-294.
Fearon, K., F. Strasser, S. D. Anker, I. Bosaeus, E. Bruera, R. L. Fainsinger, A. Jatoi, C. Loprinzi, N. MacDonald, G. Mantovani, M. Davis, M. Muscaritoli, F. Ottery, L. Radbruch, P. Ravasco, D. Walsh, A. Wilcock, S. Kaasa and V. E. Baracos (2011). "Definition and classification of cancer cachexia: an international consensus." Lancet Oncol. 12(5): 489-495.
Ferris, R. L., I. Martinez, N. Sirianni, J. Wang, A. Lopez-Albaitero, S. M. Gollin, J. T. Johnson and S. Khan (2005). "Human papillomavirus-16 associated squamous cell carcinoma of the head and neck (SCCHN): A natural disease model provides insights into viral carcinogenesis." Eur J Cancer. 41(5): 807-815.
Gay, F., Y. Estornes, J. C. Saurin, M. O. Joly-Pharaboz, E. Friederich, J. Y. Scoazec and J. Abello (2008). "In colon carcinogenesis, the cytoskeletal protein gelsolin is down-regulated during the transition from adenoma to carcinoma." Hum Pathol. 39(10): 1420-1430.
Guha, N., S. Warnakulasuriya, J. Vlaanderen and K. Straif (2014). "Betel quid chewing and the risk of oral and oropharyngeal cancers: a meta-analysis with implications for cancer control." Int J Cancer. 135(6): 1433-1443.
Haddad, J. G., K. D. Harper, M. Guoth, G. G. Pietra and J. W. Sanger (1990). "Angiopathic consequences of saturating the plasma scavenger system for actin." Proc Natl Acad Sci USA. 87(4): 1381-1385.
Haga, K., H. Fujita, M. Nomoto, A. Sazawa, K. Nakagawa, T. Harabayashi, N. Shinohara, M. Takimoto, K. Nonomura and N. Kuzumaki (2004). "Gelsolin gene silencing involving unusual hypersensitivities to dimethylsulfate and KMnO4 in vivo footprinting on its promoter region." Int J Cancer. 111(6): 873-880.
Hoffmann, T. K., G. Dworacki, T. Tsukihiro, N. Meidenbauer, W. Gooding, J. T. Johnson and T. L. Whiteside (2002). "Spontaneous apoptosis of circulating T lymphocytes in patients with head and neck cancer and its clinical importance." Clin Cancer Res. 8(8): 2553-2562.
Horvath-Szalai, Z., P. Kustan, D. Muhl, A. Ludany, B. Bugyi and T. Koszegi (2017). "Antagonistic sepsis markers: Serum gelsolin and actin/gelsolin ratio." Clin Biochem. 50(3): 127-133.
Hsieh, L. L., P. F. Wang, I. H. Chen, C. T. Liao, H. M. Wang, M. C. Chen, J. T. Chang and A. J. Cheng (2001). "Characteristics of mutations in the p53 gene in oral squamous cell carcinoma associated with betel quid chewing and cigarette smoking in Taiwanese." Carcinogenesis. 22(9): 1497-1503.
Igney, F. H. and P. H. Krammer (2005). "Tumor counterattack: fact or fiction?" Cancer Immunol, Immunother. 54(11): 1127-1136.
Imai, R., Y. Takenaka, T. Yasui, S. Nakahara, Y. Yamamoto, A. Hanamoto, N. Takemoto, T. Fukusumi, H. Cho, M. Yamamoto and H. Inohara (2015). "Prognostic significance of serum squamous cell carcinoma antigen in patients with head and neck cancer." Acta Otolaryngol. 135(3): 295-301.
Jager-Wittenaar, H., P. U. Dijkstra, G. Dijkstra, J. Bijzet, J. A. Langendijk, B. van der Laan and J. L. N. Roodenburg (2017). "High prevalence of cachexia in newly diagnosed head and neck cancer patients: An exploratory study." Nutrition. 35: 114-118.
Kamada, S., H. Kusano, H. Fujita, M. Ohtsu, R. C. Koya, N. Kuzumaki and Y. Tsujimoto (1998). "A cloning method for caspase substrates that uses the yeast two-hybrid system: Cloning of the antiapoptotic gene gelsolin." Proc Natl Acad Sci USA. 95(15): 8532-8537.
Kao, S. Y. and E. Lim (2015). "An overview of detection and screening of oral cancer in Taiwan." Chin J Dent Res. 18(1): 7-12.
Kim, J. H., Y. K. Choi, H. J. Kwon, H. K. Yang, J. H. Choi and D. Y. Kim (2004). "Downregulation of gelsolin and retinoic acid receptor beta expression in gastric cancer tissues through histone deacetylase 1." J Gastroenterol Hepatol. 19(2): 218-224.
Kothakota, S., T. Azuma, C. Reinhard, A. Klippel, J. Tang, K. Chu, T. J. McGarry, M. W. Kirschner, K. Koths, D. J. Kwiatkowski and L. T. Williams (1997). "Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis." Science. 278(5336): 294-298.
Koya, R. C., H. Fujita, S. Shimizu, M. Ohtsu, M. Takimoto, Y. Tsujimoto and N. Kuzumaki (2000). "Gelsolin inhibits apoptosis by blocking mitochondrial membrane potential loss and cytochrome c release." J Biol Chem. 275(20): 15343-15349.
Kusano, H., S. Shimizu, R. C. Koya, H. Fujita, S. Kamada, N. Kuzumaki and Y. Tsujimoto (2000). "Human gelsolin prevents apoptosis by inhibiting apoptotic mitochondrial changes via closing VDAC." Oncogene. 19(42): 4807-4814.
Kwiatkowski, D. J., R. Mehl, S. Izumo, B. Nadalginard and H. L. Yin (1988). "Muscle is the major source of plasma gelsolin." J Biol Chem. 263(17): 8239-8243.
Kwiatkowski, D. J., T. P. Stossel, S. H. Orkin, J. E. Mole, H. R. Colten and H. L. Yin (1986). "Plasma and cytoplasmic gelsolins are encoded by a single gene and contain a duplicated actin-binding domain." Nature. 323(6087): 455-458.
Lee, H. K., D. Driscoll, H. Asch, B. Asch and P. J. Zhang (1999). "Downregulated gelsolin expression in hyperplastic and neoplastic lesions of the prostate." Prostate. 40(1): 14-19.
Lee, P.-S., A. B. Waxman, K. L. Cotich, S. W. Chung, M. A. Perrella and T. P. Stossel (2007). "Plasma gelsolin is a marker and therapeutic agent in animal sepsis*." Critical Care Medicine. 35(3): 849-855.
Lee, P. S., K. Sampath, S. A. Karumanchi, H. Tamez, I. Bhan, T. Isakova, O. M. Gutierrez, M. Wolf, Y. Chang, T. P. Stossel and R. Thadhani (2009). "Plasma gelsolin and circulating actin correlate with hemodialysis mortality." J Am Soc Nephrol. 20(5): 1140-1148.
Lee, P. S., A. B. Waxman, K. L. Cotich, S. W. Chung, M. A. Perrella and T. P. Stossel (2007). "Plasma gelsolin is a marker and therapeutic agent in animal sepsis." Crit Care Med. 35(3): 849-855.
Lee, W. M. and R. M. Galbraith (1992). "The extracellular actin-scavenger system and actin toxicity." N Engl J Med. 326(20): 1335-1341.
Li, G. H., P. D. Arora, Y. Chen, C. A. McCulloch and P. Liu (2012). "Multifunctional roles of gelsolin in health and diseases." Med Res Rev. 32(5): 999-1025.
Li, W. X., M. X. Yang, X. Q. Hong, T. G. Dong, T. Yi, S. L. Lin, X. Y. Qin and W. X. Niu (2016). "Overexpression of gelsolin reduces the proliferation and invasion of colon carcinoma cells." Mol Med Rep. 14(4): 3059-3065.
Lind, S. E., D. B. Smith, P. A. Janmey and T. P. Stossel (1988). "Depression of gelsolin levels and detection of gelsolin-actin complexes in plasma of patients with acute lung injury." Am Rev Respir Dis. 138(2): 429-434.
Lucia, S., M. Esposito, F. Rossi Fanelli and M. Muscaritoli (2012). "Cancer cachexia: from molecular mechanisms to patient's care." Crit Rev Oncog. 17(3): 315-321.
Ma, X., W. Sun, J. Shen, Y. Hua, F. Yin, M. Sun and Z. Cai (2016). "Gelsolin promotes cell growth and invasion through the upregulation of p-AKT and p-P38 pathway in osteosarcoma." Tumour Biol. 37(6): 7165-7174.
Marino, N., J. C. Marshall, J. W. Collins, M. Zhou, Y. Qian, T. Veenstra and P. S. Steeg (2013). "Nm23-h1 binds to gelsolin and inactivates its actin-severing capacity to promote tumor cell motility and metastasis." Cancer Res. 73(19): 5949-5962.
Marrocco, C., S. Rinalducci, A. Mohamadkhani, G. M. D'Amici and L. Zolla (2010). "Plasma gelsolin protein: a candidate biomarker for hepatitis B-associated liver cirrhosis identified by proteomic approach." Blood Transfus. 8 Suppl 3: s105-112.
Matarrese, P., C. Abbruzzese, A. M. Mileo, R. Vona, B. Ascione, P. Visca, F. Rollo, M. Benevolo, W. Malorni and M. G. Paggi (2016). "Interaction between the human papillomavirus 16 E7 oncoprotein and gelsolin ignites cancer cell motility and invasiveness." Oncotarget. 7(32): 50972-50985.
Mielnicki, L. M., A. M. Ying, K. L. Head, H. L. Asch and B. B. Asch (1999). "Epigenetic regulation of gelsolin expression in human breast cancer cells." Exp Cell Res. 249(1): 161-176.
Ni, X. G., L. Zhou, G. Q. Wang, S. M. Liu, X. F. Bai, F. Liu, M. P. Peppelenbosch and P. Zhao (2008). "The ubiquitin-proteasome pathway mediates gelsolin protein downregulation in pancreatic cancer." Mol Med. 14(9-10): 582-589.
Noske, A., C. Denkert, H. Schober, C. Sers, B. Zhumabayeva, W. Weichert, M. Dietel and K. Wiechen (2005). "Loss of Gelsolin expression in human ovarian carcinomas." Eur J Cancer. 41(3): 461-469.
Osborn, T. M., M. Verdrengh, T. P. Stossel, A. Tarkowski and M. Bokarewa (2008). "Decreased levels of the gelsolin plasma isoform in patients with rheumatoid arthritis." Arthritis Res Ther. 10(5): R117.
Peter, M. E., A. Hadji, A. E. Murmann, S. Brockway, W. Putzbach, A. Pattanayak and P. Ceppi (2015). "The role of CD95 and CD95 ligand in cancer." Cell Death Differ. 22(4): 549-559.
Pils, D., D. Tong, G. Hager, E. Obermayr, S. Aust, G. Heinze, M. Kohl, E. Schuster, A. Wolf, J. Sehouli, I. Braicu, I. Vergote, T. Van Gorp, S. Mahner, N. Concin, P. Speiser and R. Zeillinger (2013). "A combined blood based gene expression and plasma protein abundance signature for diagnosis of epithelial ovarian cancer--a study of the OVCAD consortium." BMC Cancer. 13: 178.
Pope, B. and A. G. Weeds (1986). "Binding of pig plasma gelsolin to F-actin and partial fractionation into calcium-dependent and calcium-independent forms." Eur J Biochem. 161(1): 85-93.
Prasad, S. C., P. J. Thraves, A. Dritschilo and M. R. Kuettel (1997). "Protein expression changes associated with radiation-induced neoplastic progression of human prostate epithelial cells." Electrophoresis. 18(3-4): 629-637.
Ranuncolo, S. M., L. I. Puricelli, E. B. D. Joffe, A. H. Roffo, E. Matos, D. Loria and M. Vilensky (2003). "Circulating 92-kilodalton matrix metalloproteinase (MMP-9) activity is enhanced in the euglobulin plasma fraction of head and neck squamous cell carcinoma - Reply." Cancer. 97(1): 203-204.
Rao, J., D. Seligson, H. Visapaa, S. Horvath, M. Eeva, K. Michel, A. Pantuck, A. Belldegrun and A. Palotie (2002). "Tissue microarray analysis of cytoskeletal actin-associated biomarkers gelsolin and E-cadherin in urothelial carcinoma." Cancer. 95(6): 1247-1257.
Roopenian, D. C., V. Aidinis, P. Carninci, M. Armaka, W. Witke, V. Harokopos, N. Pavelka, D. Koczan, C. Argyropoulos, M.-M. Thwin, S. Möller, W. Kazunori, P. Gopalakrishnakone, P. Ricciardi-Castagnoli, H.-J. Thiesen, Y. Hayashizaki and G. Kollias (2005). "Cytoskeletal Rearrangements in Synovial Fibroblasts as a NovelPathophysiological Determinant of Modeled Rheumatoid Arthritis." PLoS Genet. 1(4): e48.
Rosas, S. L., W. Koch, M. G. da Costa Carvalho, L. Wu, J. Califano, W. Westra, J. Jen and D. Sidransky (2001). "Promoter hypermethylation patterns of p16, O6-methylguanine-DNA-methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients." Cancer Res. 61(3): 939-942.
Shieh, D. B., I. W. Chen, T. Y. Wei, C. Y. Shao, H. J. Chang, C. H. Chung, T. Y. Wong and Y. T. Jin (2006). "Tissue expression of gelsolin in oral carcinogenesis progression and its clinicopathological implications." Oral Oncol. 42(6): 599-606.
Shieh, D. B., J. Godleski, J. E. Herndon, 2nd, T. Azuma, H. Mercer, D. J. Sugarbaker and D. J. Kwiatkowski (1999). "Cell motility as a prognostic factor in Stage I nonsmall cell lung carcinoma: the role of gelsolin expression." Cancer. 85(1): 47-57.
Siriwardena, S., T. Tsunematsu, G. Qi, N. Ishimaru and Y. Kudo (2018). "Invasion-related factors as potential diagnostic and therapeutic targets in oral squamous cell carcinoma-a review." Int J Mol Sci. 19(5).
Smith, D. B., P. A. Janmey, J. A. Sherwood, R. J. Howard and S. E. Lind (1988). "Decreased plasma gelsolin levels in patients with plasmodium falciparum malaria: a consequence of hemolysis?" Blood. 72(1): 214-218.
Suhler, E., W. Lin, H. L. Yin and W. M. Lee (1997). "Decreased plasma gelsolin concentrations in acute liver failure, myocardial infarction, septic shock, and myonecrosis." Crit Care Med. 25(4): 594-598.
Sun, H. Q., M. Yamamoto, M. Mejillano and H. L. Yin (1999). "Gelsolin, a multifunctional actin regulatory protein." J Biol Chem. 274(47): 33179-33182.
Tanaka, H., R. Shirkoohi, K. Nakagawa, H. Qiao, H. Fujita, F. Okada, J. Hamada, S. Kuzumaki, M. Takimoto and N. Kuzumaki (2006). "siRNA gelsolin knockdown induces epithelial-mesenchymal transition with a cadherin switch in human mammary epithelial cells." Int J Cancer. 118(7): 1680-1691.
Tanaka, M., L. Mullauer, Y. Ogiso, H. Fujita, S. Moriya, K. Furuuchi, T. Harabayashi, N. Shinohara, T. Koyanagi and N. Kuzumaki (1995). "Gelsolin: a candidate for suppressor of human bladder cancer." Cancer Res. 55(15): 3228-3232.
Toomey, D., H. P. Redmond and D. Bouchier-Hayes (1995). "Mechanisms mediating cancer cachexia." Cancer. 76(12): 2418-2426.
Vandekerckhove, J. (1990). "Actin-binding proteins." Curr Opin Cell Biol. 2(1): 41-50.
Vasconcellos, C. A. and S. E. Lind (1993). "Coordinated inhibition of actin-induced platelet aggregation by plasma gelsolin and vitamin D-binding protein." Blood. 82(12): 3648-3657.
Visapaa, H., M. Bui, Y. Huang, D. Seligson, H. Tsai, A. Pantuck, R. Figlin, J. Y. Rao, A. Belldegrun, S. Horvath and A. Palotie (2003). "Correlation of Ki-67 and gelsolin expression to clinical outcome in renal clear cell carcinoma." Urology. 61(4): 845-850.
Wang, H., B. Cheng, Q. Chen, S. Wu, C. Lv, G. Xie, Y. Jin and X. Fang (2008). "Time course of plasma gelsolin concentrations during severe sepsis in critically ill surgical patients." Crit Care. 12(4): R106.
Wang, P. W., M. R. Abedini, L. X. Yang, A. A. Ding, D. Figeys, J. Y. Chang, B. K. Tsang and D. B. Shieh (2014). "Gelsolin regulates cisplatin sensitivity in human head-and-neck cancer." Int J Cancer. 135(12): 2760-2769.
Winston, J. S., H. L. Asch, P. J. Zhang, S. B. Edge, A. Hyland and B. B. Asch (2001). "Downregulation of gelsolin correlates with the progression to breast carcinoma." Breast Cancer Res Treat. 65(1): 11-21.
Yamaguchi, H. and J. Condeelis (2007). "Regulation of the actin cytoskeleton in cancer cell migration and invasion." Biochim Biophys Acta. 1773(5): 642-652.
Yang, J., D. Tan, H. L. Asch, H. Swede, G. Bepler, J. Geradts and K. B. Moysich (2004). "Prognostic significance of gelsolin expression level and variability in non-small cell lung cancer." Lung Cancer. 46(1): 29-42.
Yin, H. L. and T. P. Stossel (1979). "Control of cytoplasmic actin gel-sol transformation by gelsolin, a calcium-dependent regulatory protein." Nature. 281(5732): 583-586.
Yu, J. S., Y. T. Chen, W. F. Chiang, Y. C. Hsiao, L. J. Chu, L. C. See, C. S. Wu, H. T. Tu, H. W. Chen, C. C. Chen, W. C. Liao, Y. T. Chang, C. C. Wu, C. Y. Lin, S. Y. Liu, S. T. Chiou, S. L. Chia, K. P. Chang, C. Y. Chien, S. W. Chang, C. J. Chang, J. D. Young, C. C. Pao, Y. S. Chang and L. H. Hartwell (2016). "Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan." Proc Natl Acad Sci USA. 113(41): 11549-11554.
Zhuo, J., E. H. Tan, B. Yan, L. Tochhawng, M. Jayapal, S. Koh, H. K. Tay, S. K. Maciver, S. C. Hooi, M. Salto-Tellez, A. P. Kumar, Y. C. Goh, Y. C. Lim and C. T. Yap (2012). "Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade." PLoS One. 7(8): e43594.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2025-08-01起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2025-08-01起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw