抗血管與化學治療通過載藥之聲學奈米滴運用於腫瘤診斷與治療

簡易檢索 / 詳目顯示

回結果列表

研究生：	何奕儒 Ho, Yi Ju
論文名稱：	抗血管與化學治療通過載藥之聲學奈米滴運用於腫瘤診斷與治療 Anti-Vascular and Chemical Therapy by Drug-Loaded Acoustic Nanodroplets for Tumor Theranostics
指導教授：	葉秩光 Yeh, Chih Kuang
口試委員:	田雨生江啟勳林政鞍張建文
學位類別：	博士 Doctor
系所名稱：	原子科學院 - 生醫工程與環境科學系 Department of Biomedical Engineering and Environmental Sciences
論文出版年：	2017
畢業學年度：	105
語文別：	英文
論文頁數：	135
中文關鍵詞：	奈米液滴、聲學液滴汽化、抗血管治療、藥物滲透、診斷治療應用
外文關鍵詞：	nanodroplet, acoustic droplet vaporization, anti-vascular therapy, drug penetration, theranostic application
相關次數：	點閱：3 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

抗血管治療主要以血管破裂藥劑或超音波刺激微氣泡破裂的方式，直接造成不正常的腫瘤血管破裂，進而餓死腫瘤細胞達到治療效果。抗血管治療與化學治療的結合運用，能藉由血管破裂打破腫瘤微環境造成的障蔽，有效提升藥物滲透並抑制腫瘤生長。聲學相變奈米液滴具有液態內核，相較於氣態的微氣泡，可提升體內存活時間與載藥的穩定性。當載藥奈米液滴受到超音波刺激時，核中的液體會轉變成氣體，此聲學液滴汽化的現象，同步產生超音波對比影像與藥物遞送，提供醫學研究中診斷治療的應用。此外，聲學液滴汽化過程中產生的機械力，會對血管內皮細胞產生生物效應，提供了一種新的並具有潛力的方式去進行抗血管治療。本論文欲利用聲學液滴汽化達到抗血管治療的效果，並評估治療後腫瘤內部的血流灌注、藥物滲透與細胞生物效應。首先，第二章中評估了聲學液滴汽化造成腫瘤血管破裂，並提升奈米粒子滲透的可行性。比較微米與奈米尺寸之液滴汽化，奈米液滴擁有較長的有效治療時間，可持續地擊破血管並提升奈米粒子的滲透。組織內的聲學液滴汽化與氣泡進行穴蝕效應產生的機械力，可擴展奈米粒子的滲透距離，以提升瘤內分布的均勻性。第二部分主要陳述於第三章，運用載藥奈米液滴汽化，同時進行抗血管治療與化學治療。超音波對比影像於診斷治療的運用中，顯示治療過程中，聲學液滴汽化即時發生的位置，與隨後導致的腫瘤灌注下降。結合治療可於腫瘤中心區域產生血管破裂，並於腫瘤中心與邊緣區域進行藥物滲透，以瘤內的空間合作相互補償單一治療時的抗性。於第四章中主要研究聲學液滴汽化產生之氣泡，於組織中受到超音波刺激後所產生的行為，進而評估氣泡於腫瘤組織中，位移置血流灌注貧乏區域的可行性。活體影像證實組織中的氣泡可經由超音波刺激，被推動至遠離鄰近血管的遠端組織並產生穴蝕效應。體外實驗顯示氣泡的形成與位移可導致細胞膜損傷，並提出組織內聲學液滴汽化產生之氣泡，藉由物理治療直接傷害腫瘤細胞的能力。因此，本論文證實了以聲學液滴汽化，進行抗血管治療並提升藥物滲透的可行性，並評估奈米液滴於腫瘤血管與組織中，同步進行診斷與治療的運用，此研究成果將於未來聲學液滴汽化的醫療發展中提供有價值的資訊。

Anti-vascular therapy directly causes abnormal tumor vessel disruption to starve tumor cells by using vascular disrupting agents (VDAs) and ultrasound stimulated microbubble destruction (USMD). Combining anti-vascular therapy and chemotherapy, vascular disruption can break the barrier of tumor microenvironments to improve drug penetration and further inhibit tumor growth. Acoustic phase-changed nanodroplets contain with liquid core to improve the in vivo lifetime and drug-loaded stability than gaseous microbubbles. When drug-loaded nanodroplets receive ultrasound stimulation, liquid core will be vaporized to gaseous phase to form bubbles and release drugs. This phenomenon of acoustic droplet vaporization (ADV) simultaneously produces ultrasound contrast imaging and drug delivery to provide theranostic applications in medical research. Furthermore, the process of ADV also produces mechanical force to induce bioeffect on vascular endothelial cells, which might be a novel and potential strategy for anti-vascular therapy. This thesis tried to induce anti-vascular therapy by ADV and evaluate the intratumoral blood perfusion, drug penetration, and cellular bioeffects after treatment. Firstly, the feasibility of using ADV to disrupt vessel wall and improve the nanoparticle penetration in solid tumors was evaluated in chapter 2. Comparison with micro- and nano-sized droplet vaporization, nanodroplets showed longer effective treatment time to continuously disrupt vessels and improve nanoparticle penetration. Moreover, the mechanical force induced by intertissue ADV and ADV-generated bubble (ADV-B) cavitation can extend the penetration distance of nanoparticles to improve the uniformity of intratumoral distribution. The second part presented in chapter 3 attempted to use drug-loaded nanodroplet vaporization to produce anti-vascular therapy and chemotherapy simultaneously. Ultrasound contrast imaging indicated the real-time location of ADV occurring during treatment and the subsequent reduction of tumor perfusion for theranostic applications. The intratumoral spatial cooperation of combination therapy revealed vascular disruption in the central region and drug penetration in both central and peripheral region to complement the treatment resistance of each other. In chapter 4, the behaviors of intertissue ADV-Bs were investigated to assess the feasibility of moving intertissue ADV-Bs into the poorly perfused regions of solid tumors. Intravital imaging demonstrated intertissue ADV-Bs can be pushed to distant tissue away from the adjacent vessels and activated for cavitation by ultrasound stimulation. The in vitro experiments revealed cell membrane damage induced by ADV-B formation and movement, which proposed a potential ability of intertissue ADV-Bs to directly damage tumor cells by physical therapy. Therefore, this thesis demonstrated the feasibility for achieving anti-vascular therapy and improving drug penetration by ADV, and evaluated the theranostic applications for nanodroplets in tumor vessels and tissue. These results provided valuable information for medical development of ADV in future.

中文摘要        I
Abstract        III
致謝        V
List of Figures    VII
List of Tables    XI
Chapter 1.        1
Introduction    1
1.    Correlation between Tumor Microenvironment and Drug Penetration    1
1.1.    Abnormal Tumor Microenvironment    1
1.2.    Specific Morphology of Tumor Vessels    2
1.3.    Drug Penetration in Tumor Microenvironment    4
2.    Anti-Vascular Therapy    7
2.1.    Accompanied Anti-Vascular Effect in Cancer Therapy    7
2.2.    Vascular Disrupting Agents (VDAs)    8
2.3.    Considerations of VDAs    11
2.4.    Combination Therapy with VDAs    13
3.    Ultrasound Stimulated Microbubble Destruction (USMD)    15
3.1.    Biological Effects by Bubble Cavitation    15
3.2.    Development of USMD for Anti-Vascular Therapy    17
3.3.    Acoustic Droplet Vaporization (ADV)    24
4.    Scope and Organization of This Dissertation    25
Chapter 2.        28
Improving Nanoparticle Penetration in Tumors by Vascular Disruption with Acoustic Droplet Vaporization    28
1.    Introduction    28
2.    Method    29
2.1.    Preparation of Particles    29
2.2.    Cell Culture and Animal Preparation    31
2.3.    Intravital Imaging Using the Acousto-optical System    33
2.4.    Quantification of Penetration    35
2.5.    Ultrasound Sonication of Solid Tumors    36
2.6.    Histological Assessments    37
2.7.    Statistical Analysis    39
3.    Result    39
3.1.    Size Distribution of Particles    39
3.2.    Quantification of Penetration    40
3.3.    Extravascular Transport Distance    43
3.4.    Solid-Tumor Histology    44
4.    Summary    45
Chapter 3.        47
Concurrent Anti-Vascular Therapy and Chemotherapy in Solid Tumors Using Drug-Loaded Acoustic Nanodroplet Vaporization    47
1.    Introduction    47
2.    Method    49
2.1.    Materials    49
2.2.    Preparation of DOX-NDs    50
2.3.    Characterization of DOX-NDs    50
2.4.    Acousto-Optical System    52
2.5.    Cytotoxicity of DOX-NDs with US Sonication    52
2.6.    Intravital Images of DOX-NDs Vaporization    54
2.7.    Solid Tumor Treatment and Perfusion Analysis    57
2.8.    Immunohistochemical Assessment    60
2.9.    Tumor Size Tracing and Mice Survival    61
2.10.    Statistical Evaluation    62
3.    Result    63
3.1.    Characterization of DOX-NDs    63
3.2.    Cell Viability of DOX-NDs Vaporization    64
3.3.    Extravascular DOX-NDs Distribution    67
3.4.    Vascular Responses Induced by ADV.    70
3.5.    Alteration of Tumor Perfusion after Treatment    72
3.6.    Intratumoral Drug Distribution and Tissue Necrosis    75
3.7.    Therapeutic Efficacy    77
4.    Summary    79
Chapter 4.        80
Theranostic Performance of Acoustic Nanodroplet Vaporization-Generated Bubbles in Tumor Intertissue    80
1.    Introduction    80
2.    Method    82
2.1.    Materials    82
2.2.    Characterization of DiI-NDs    83
2.3.    Intertissue Behavior of ADV-Bs During US Stimulation    85
2.4.    Cellular Bioeffect by ADV and ADV-B Movement    86
2.5.    Intertissue ADV-B Movement within Solid Tumors    88
2.6.    Histological Assessments    89
2.7.    Statistical Evaluation    89
3.    Result    90
3.1.    Characterization of DiI-NDs    90
3.2.    Formation, Movement, and Cavitation of Intertissue ADV-Bs    92
3.3.    Cellular Bioeffects with ADV and ADV-B Movement    94
3.4.    Intratumoral ADV-B Movement    95
3.5.    Histological Assessment    98
4.    Summary    99
Chapter 5.        101
Discussion        101
1.    Improving Nanoparticle Penetration in Tumors by Vascular Disruption with Acoustic Droplet Vaporization    101
2.    Concurrent Anti-Vascular Therapy and Chemotherapy in Solid Tumors Using Drug-Loaded Acoustic Nanodroplet Vaporization    105
3.    Theranostic Performance of Acoustic Nanodroplet Vaporization-Generated Bubbles in Tumor Intertissue    110
4.    Comparison with USMD and ADV    111
Chapter 6.        116
Conclusion and Future Work    116
Reference        118
Author biography    134
Publication List    134


                                

[1] G.I. Evan, K.H. Vousden, Proliferation, cell cycle and apoptosis in cancer, Nature, 411 (2001) 342-348.
[2] J. Folkman, Anti-angiogenesis: new concept for therapy of solid tumors, Ann Surg, 175 (1972) 409-416.
[3] J. Folkman, Angiogenesis in psoriasis: therapeutic implications, J Invest Dermatol, 59 (1972) 40-43.
[4] S. Azzi, J.K. Hebda, J. Gavard, Vascular permeability and drug delivery in cancers, Front Oncol, 3 (2013) 211.
[5] P. Carmeliet, Mechanisms of angiogenesis and arteriogenesis, Nat Med, 6 (2000) 389-395.
[6] R.K. Jain, T. Stylianopoulos, Delivering nanomedicine to solid tumors, Nat Rev Clin Oncol, 7 (2010) 653-664.
[7] T.P. Padera, B.R. Stoll, J.B. Tooredman, D. Capen, E. di Tomaso, R.K. Jain, Pathology: cancer cells compress intratumour vessels, Nature, 427 (2004) 695.
[8] D. Fukumura, R.K. Jain, Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize, J Cell Biochem, 101 (2007) 937-949.
[9] S.H. Jang, M.G. Wientjes, D. Lu, J.L. Au, Drug delivery and transport to solid tumors, Pharm Res, 20 (2003) 1337-1350.
[10] S.K. Sriraman, B. Aryasomayajula, V.P. Torchilin, Barriers to drug delivery in solid tumors, Tissue Barriers, 2 (2014) e29528.
[11] M. Egeblad, M.G. Rasch, V.M. Weaver, Dynamic interplay between the collagen scaffold and tumor evolution, Current Opinion in Cell Biology, 22 (2010) 697-706.
[12] C. Frantz, K.M. Stewart, V.M. Weaver, The extracellular matrix at a glance, Journal of Cell Science, 123 (2010) 4195-4200.
[13] J.W. Nichols, Y.H. Bae, Odyssey of a cancer nanoparticle: from injection site to site of action, Nano Today, 7 (2012) 606-618.
[14] J.W. Wojtkowiak, D. Verduzco, K.J. Schramm, R.J. Gillies, Drug resistance and cellular adaptation to tumor acidic pH microenvironment, Mol Pharm, 8 (2011) 2032-2038.
[15] P. Vaupel, L. Harrison, Tumor hypoxia: causative factors, compensatory mechanisms, and cellular response, Oncologist, 9 Suppl 5 (2004) 4-9.
[16] W. Risau, I. Flamme, Vasculogenesis, Annual Review of Cell and Developmental Biology, 11 (1995) 73-91.
[17] J.M. Isner, T. Asahara, Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization, J Clin Invest, 103 (1999) 1231-1236.
[18] R.K. Jain, Molecular regulation of vessel maturation, Nat Med, 9 (2003) 685-693.
[19] J. Fang, H. Nakamura, H. Maeda, The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect, Adv Drug Deliv Rev, 63 (2011) 136-151.
[20] A.K. Iyer, G. Khaled, J. Fang, H. Maeda, Exploiting the enhanced permeability and retention effect for tumor targeting, Drug Discov Today, 11 (2006) 812-818.
[21] P.U. Atukorale, G. Covarrubias, L. Bauer, E. Karathanasis, Vascular targeting of nanoparticles for molecular imaging of diseased endothelium, Adv Drug Deliv Rev, (2016).
[22] S. Morikawa, P. Baluk, T. Kaidoh, A. Haskell, R.K. Jain, D.M. McDonald, Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors, Am J Pathol, 160 (2002) 985-1000.
[23] L. Zhang, H. Nishihara, M.R. Kano, Pericyte-coverage of human tumor vasculature and nanoparticle permeability, Biol Pharm Bull, 35 (2012) 761-766.
[24] G.K. Owens, M.S. Kumar, B.R. Wamhoff, Molecular regulation of vascular smooth muscle cell differentiation in development and disease, Physiol Rev, 84 (2004) 767-801.
[25] P. Baluk, S. Morikawa, A. Haskell, M. Mancuso, D.M. McDonald, Abnormalities of basement membrane on blood vessels and endothelial sprouts in tumors, Am J Pathol, 163 (2003) 1801-1815.
[26] L. Nguyen, T. Fifis, C. Malcontenti-Wilson, L.S. Chan, P.N. Costa, M. Nikfarjam, V. Muralidharan, C. Christophi, Spatial morphological and molecular differences within solid tumors may contribute to the failure of vascular disruptive agent treatments, BMC Cancer, 12 (2012) 522.
[27] Y. Li, J. Wang, M.G. Wientjes, J.L. Au, Delivery of nanomedicines to extracellular and intracellular compartments of a solid tumor, Adv Drug Deliv Rev, 64 (2012) 29-39.
[28] T. Stylianopoulos, J.D. Martin, M. Snuderl, F. Mpekris, S.R. Jain, R.K. Jain, Coevolution of solid stress and interstitial fluid pressure in tumors during progression: implications for vascular collapse, Cancer Res, 73 (2013) 3833-3841.
[29] Y. Nakamura, A. Mochida, P.L. Choyke, H. Kobayashi, Nanodrug Delivery: Is the Enhanced Permeability and Retention Effect Sufficient for Curing Cancer?, Bioconjug Chem, 27 (2016) 2225-2238.
[30] J.R. Less, T.C. Skalak, E.M. Sevick, R.K. Jain, Microvascular architecture in a mammary carcinoma: branching patterns and vessel dimensions, Cancer Res, 51 (1991) 265-273.
[31] J. Wang, Z. Zhao, S. Shen, C. Zhang, S. Guo, Y. Lu, Y. Chen, W. Liao, Y. Liao, J. Bin, Selective depletion of tumor neovasculature by microbubble destruction with appropriate ultrasound pressure, Int J Cancer, 137 (2015) 2478-2491.
[32] G.M. Tozer, C. Kanthou, B.C. Baguley, Disrupting tumour blood vessels, Nat Rev Cancer, 5 (2005) 423-435.
[33] J. Ehling, B. Theek, F. Gremse, S. Baetke, D. Mockel, J. Maynard, S.A. Ricketts, H. Grull, M. Neeman, R. Knuechel, W. Lederle, F. Kiessling, T. Lammers, Micro-CT imaging of tumor angiogenesis: quantitative measures describing micromorphology and vascularization, Am J Pathol, 184 (2014) 431-441.
[34] H. Kobayashi, R. Watanabe, P.L. Choyke, Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target?, Theranostics, 4 (2013) 81-89.
[35] F. Danhier, O. Feron, V. Preat, To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery, J Control Release, 148 (2010) 135-146.
[36] C.H. Heldin, K. Rubin, K. Pietras, A. Ostman, High interstitial fluid pressure - an obstacle in cancer therapy, Nat Rev Cancer, 4 (2004) 806-813.
[37] J. Lankelma, H. Dekker, F.R. Luque, S. Luykx, K. Hoekman, P. van der Valk, P.J. van Diest, H.M. Pinedo, Doxorubicin gradients in human breast cancer, Clin Cancer Res, 5 (1999) 1703-1707.
[38] B. Haley, E. Frenkel, Nanoparticles for drug delivery in cancer treatment, Urologic Oncology-Seminars and Original Investigations, 26 (2008) 57-64.
[39] T.M. Allen, P.R. Cullis, Drug delivery systems: entering the mainstream, Science, 303 (2004) 1818-1822.
[40] S.M. Janib, A.S. Moses, J.A. MacKay, Imaging and drug delivery using theranostic nanoparticles, Adv Drug Deliv Rev, 62 (2010) 1052-1063.
[41] J. Liu, Y. Huang, A. Kumar, A. Tan, S. Jin, A. Mozhi, X.J. Liang, pH-sensitive nano-systems for drug delivery in cancer therapy, Biotechnol Adv, 32 (2014) 693-710.
[42] N. Rapoport, Phase-shift, stimuli-responsive perfluorocarbon nanodroplets for drug delivery to cancer, Wiley Interdiscip Rev Nanomed Nanobiotechnol, 4 (2012) 492-510.
[43] Y. Matsumura, H. Maeda, A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs, Cancer Res, 46 (1986) 6387-6392.
[44] F. Yuan, M. Dellian, D. Fukumura, M. Leunig, D.A. Berk, V.P. Torchilin, R.K. Jain, Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size, Cancer Res, 55 (1995) 3752-3756.
[45] R. Duncan, Polymer conjugates for tumour targeting and intracytoplasmic delivery. The EPR effect as a common gateway?, Pharm Sci Technolo Today, 2 (1999) 441-449.
[46] A.I. Minchinton, I.F. Tannock, Drug penetration in solid tumours, Nat Rev Cancer, 6 (2006) 583-592.
[47] S.K. Hobbs, W.L. Monsky, F. Yuan, W.G. Roberts, L. Griffith, V.P. Torchilin, R.K. Jain, Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment, Proc Natl Acad Sci U S A, 95 (1998) 4607-4612.
[48] K. Ogawara, K. Un, K. Minato, K. Tanaka, K. Higaki, T. Kimura, Determinants for in vivo anti-tumor effects of PEG liposomal doxorubicin: importance of vascular permeability within tumors, Int J Pharm, 359 (2008) 234-240.
[49] H. Cabral, Y. Matsumoto, K. Mizuno, Q. Chen, M. Murakami, M. Kimura, Y. Terada, M.R. Kano, K. Miyazono, M. Uesaka, N. Nishiyama, K. Kataoka, Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size, Nat Nanotechnol, 6 (2011) 815-823.
[50] M.A. Swartz, A.W. Lund, Lymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity, Nat Rev Cancer, 12 (2012) 210-219.
[51] A.J. Primeau, A. Rendon, D. Hedley, L. Lilge, I.F. Tannock, The distribution of the anticancer drug Doxorubicin in relation to blood vessels in solid tumors, Clin Cancer Res, 11 (2005) 8782-8788.
[52] A. Rapisarda, G. Melillo, Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies, Drug Resist Updat, 12 (2009) 74-80.
[53] P. Vaupel, The role of hypoxia-induced factors in tumor progression, Oncologist, 9 Suppl 5 (2004) 10-17.
[54] O. Tredan, C.M. Galmarini, K. Patel, I.F. Tannock, Drug resistance and the solid tumor microenvironment, J Natl Cancer Inst, 99 (2007) 1441-1454.
[55] Y. Kubota, Tumor angiogenesis and anti-angiogenic therapy, Keio J Med, 61 (2012) 47-56.
[56] N. Ferrara, R.S. Kerbel, Angiogenesis as a therapeutic target, Nature, 438 (2005) 967-974.
[57] L.M. Ellis, D.J. Hicklin, VEGF-targeted therapy: mechanisms of anti-tumour activity, Nat Rev Cancer, 8 (2008) 579-591.
[58] P.C. Brooks, R.A. Clark, D.A. Cheresh, Requirement of vascular integrin alpha v beta 3 for angiogenesis, Science, 264 (1994) 569-571.
[59] J. Denekamp, Vascular Attack as a Therapeutic Strategy for Cancer, Cancer and Metastasis Reviews, 9 (1990) 267-282.
[60] D.L. Liu, S. Andersson-Engels, C. Sturesson, K. Svanberg, C.H. Hakansson, S. Svanberg, Tumour vessel damage resulting from laser-induced hyperthermia alone and in combination with photodynamic therapy, Cancer Lett, 111 (1997) 157-165.
[61] K. Hynynen, A.H. Chung, V. Colucci, F.A. Jolesz, Potential adverse effects of high-intensity focused ultrasound exposure on blood vessels in vivo, Ultrasound Med Biol, 22 (1996) 193-201.
[62] R. Ackroyd, C. Kelty, N. Brown, M. Reed, The history of photodetection and photodynamic therapy, Photochem Photobiol, 74 (2001) 656-669.
[63] W.M. Star, H.P. Marijnissen, A.E. van den Berg-Blok, J.A. Versteeg, K.A. Franken, H.S. Reinhold, Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers, Cancer Res, 46 (1986) 2532-2540.
[64] B. Chen, B.W. Pogue, J.M. Luna, R.L. Hardman, P.J. Hoopes, T. Hasan, Tumor vascular permeabilization by vascular-targeting photosensitization: effects, mechanism, and therapeutic implications, Clin Cancer Res, 12 (2006) 917-923.
[65] P. Agostinis, K. Berg, K.A. Cengel, T.H. Foster, A.W. Girotti, S.O. Gollnick, S.M. Hahn, M.R. Hamblin, A. Juzeniene, D. Kessel, M. Korbelik, J. Moan, P. Mroz, D. Nowis, J. Piette, B.C. Wilson, J. Golab, Photodynamic therapy of cancer: an update, CA Cancer J Clin, 61 (2011) 250-281.
[66] J.W. Lippert, 3rd, Vascular disrupting agents, Bioorg Med Chem, 15 (2007) 605-615.
[67] P. sideHinnen, F.A. Eskens, Vascular disrupting agents in clinical development, Br J Cancer, 96 (2007) 1159-1165.
[68] D.L. Miller, Overview of experimental studies of biological effects of medical ultrasound caused by gas body activation and inertial cavitation, Prog Biophys Mol Biol, 93 (2007) 314-330.
[69] M.E. Eichhorn, S. Strieth, M. Dellian, Anti-vascular tumor therapy: recent advances, pitfalls and clinical perspectives, Drug Resist Updat, 7 (2004) 125-138.
[70] A.M. Gaya, G.J. Rustin, Vascular disrupting agents: a new class of drug in cancer therapy, Clin Oncol (R Coll Radiol), 17 (2005) 277-290.
[71] M.S. Gee, W.N. Procopio, S. Makonnen, M.D. Feldman, N.M. Yeilding, W.M. Lee, Tumor vessel development and maturation impose limits on the effectiveness of anti-vascular therapy, Am J Pathol, 162 (2003) 183-193.
[72] I. Mitrus, A. Sochanik, T. Cichon, S. Szala, Combination of combretastatin A4 phosphate and doxorubicin-containing liposomes affects growth of B16-F10 tumors, Acta Biochim Pol, 56 (2009) 161-165.
[73] C.Y. Lin, H.C. Tseng, H.R. Shiu, M.F. Wu, C.Y. Chou, W.L. Lin, Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug, Int J Nanomedicine, 7 (2012) 2143-2152.
[74] J. Denekamp, Endothelial Cell-Proliferation as a Novel-Approach to Targeting Tumor-Therapy, Br J Cancer, 45 (1982) 136-139.
[75] G.M. Tozer, V.E. Prise, J. Wilson, M. Cemazar, S. Shan, M.W. Dewhirst, P.R. Barber, B. Vojnovic, D.J. Chaplin, Mechanisms associated with tumor vascular shut-down induced by combretastatin A-4 phosphate: intravital microscopy and measurement of vascular permeability, Cancer Res, 61 (2001) 6413-6422.
[76] Y. Sheng, J. Hua, K.G. Pinney, C.M. Garner, R.R. Kane, J.A. Prezioso, D.J. Chaplin, K. Edvardsen, Combretastatin family member OXI4503 induces tumor vascular collapse through the induction of endothelial apoptosis, Int J Cancer, 111 (2004) 604-610.
[77] M. Seshadri, J.A. Spernyak, P.G. Maiery, R.T. Cheney, R. Mazurchuk, D.A. Bellnier, Visualizing the acute effects of vascular-targeted therapy in vivo using intravital microscopy and magnetic resonance imaging: correlation with endothelial apoptosis, cytokine induction, and treatment outcome, Neoplasia, 9 (2007) 128-135.
[78] B.C. Baguley, L.M. Ching, DMXAA: an antivascular agent with multiple host responses, Int J Radiat Oncol Biol Phys, 54 (2002) 1503-1511.
[79] E.B. Garon, J.D. Neidhart, N.Y. Gabrail, M.R. de Oliveira, J. Balkissoon, F. Kabbinavar, A randomized Phase II trial of the tumor vascular disrupting agent CA4P (fosbretabulin tromethamine) with carboplatin, paclitaxel, and bevacizumab in advanced nonsquamous non-small-cell lung cancer, Onco Targets Ther, 9 (2016) 7275-7283.
[80] D.W. Siemann, M.R. Horsman, Vascular targeted therapies in oncology, Cell Tissue Res, 335 (2009) 241-248.
[81] S.T. Pan, Z.W. Zhou, Z.X. He, X. Zhang, T. Yang, Y.X. Yang, D. Wang, J.X. Qiu, S.F. Zhou, Proteomic response to 5,6-dimethylxanthenone 4-acetic acid (DMXAA, vadimezan) in human non-small cell lung cancer A549 cells determined by the stable-isotope labeling by amino acids in cell culture (SILAC) approach, Drug Des Devel Ther, 9 (2015) 937-968.
[82] D.A. Beauregard, R.B. Pedley, S.A. Hill, K.M. Brindle, Differential sensitivity of two adenocarcinoma xenografts to the anti-vascular drugs combretastatin A4 phosphate and 5,6-dimethylxanthenone-4-acetic acid, assessed using MRI and MRS, Nmr in Biomedicine, 15 (2002) 99-105.
[83] E. El-Emir, G.M. Boxer, I.A. Petrie, R.W. Boden, J.L. Dearling, R.H. Begent, R.B. Pedley, Tumour parameters affected by combretastatin A-4 phosphate therapy in a human colorectal xenograft model in nude mice, Eur J Cancer, 41 (2005) 799-806.
[84] S.P. Robinson, D.J. McIntyre, D. Checkley, J.J. Tessier, F.A. Howe, J.R. Griffiths, S.E. Ashton, A.J. Ryan, D.C. Blakey, J.C. Waterton, Tumour dose response to the antivascular agent ZD6126 assessed by magnetic resonance imaging, Br J Cancer, 88 (2003) 1592-1597.
[85] D.C. Blakey, F.R. Westwood, M. Walker, G.D. Hughes, P.D. Davis, S.E. Ashton, A.J. Ryan, Antitumor activity of the novel vascular targeting agent ZD6126 in a panel of tumor models, Clin Cancer Res, 8 (2002) 1974-1983.
[86] A.M. Shannon, D.J. Bouchier-Hayes, C.M. Condron, D. Toomey, Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies, Cancer Treat Rev, 29 (2003) 297-307.
[87] B.G. Siim, A.E. Lee, S. Shalah-Zwain, F.B. Pruijn, M.J. McKeage, W.R. Wilson, Marked potentiation of the antitumour activity of chemotherapeutic drugs by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA), Cancer Chemotherapy and Pharmacology, 51 (2003) 43-52.
[88] D.W. Siemann, E. Mercer, S. Lepler, A.M. Rojiani, Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy, Int J Cancer, 99 (2002) 1-6.
[89] P.R. Wachsberger, R. Burd, N. Marero, C. Daskalakis, A. Ryan, P. McCue, A.P. Dicker, Effect of the tumor vascular-damaging agent, ZD6126, on the radioresponse of U87 glioblastoma, Clin Cancer Res, 11 (2005) 835-842.
[90] S. Qin, C.F. Caskey, K.W. Ferrara, Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering, Phys Med Biol, 54 (2009) R27-57.
[91] C.H. Wang, C.K. Yeh, Controlling the size distribution of lipid-coated bubbles via fluidity regulation, Ultrasound Med Biol, 39 (2013) 882-892.
[92] N. Elie, A. Kaliski, P. Peronneau, P. Opolon, A. Roche, N. Lassau, Methodology for quantifying interactions between perfusion evaluated by DCE-US and hypoxia throughout tumor growth, Ultrasound Med Biol, 33 (2007) 549-560.
[93] C.R. Anderson, X. Hu, H. Zhang, J. Tlaxca, A.E. Decleves, R. Houghtaling, K. Sharma, M. Lawrence, K.W. Ferrara, J.J. Rychak, Ultrasound molecular imaging of tumor angiogenesis with an integrin targeted microbubble contrast agent, Invest Radiol, 46 (2011) 215-224.
[94] K. Ferrara, R. Pollard, M. Borden, Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery, Annu Rev Biomed Eng, 9 (2007) 415-447.
[95] G. ter Haar, Safety and bio-effects of ultrasound contrast agents, Med Biol Eng Comput, 47 (2009) 893-900.
[96] I. Lentacker, I. De Cock, R. Deckers, S.C. De Smedt, C.T. Moonen, Understanding ultrasound induced sonoporation: definitions and underlying mechanisms, Adv Drug Deliv Rev, 72 (2014) 49-64.
[97] J. Wu, J.P. Ross, J.F. Chiu, Reparable sonoporation generated by microstreaming, J Acoust Soc Am, 111 (2002) 1460-1464.
[98] N. Kudo, K. Okada, K. Yamamoto, Sonoporation by single-shot pulsed ultrasound with microbubbles adjacent to cells, Biophys J, 96 (2009) 4866-4876.
[99] P. Prentice, A. Cuschierp, K. Dholakia, M. Prausnitz, P. Campbell, Membrane disruption by optically controlled microbubble cavitation, Nature Physics, 1 (2005) 107-110.
[100] I. Skachkov, Y. Luan, A.F. van der Steen, N. de Jong, K. Kooiman, Targeted microbubble mediated sonoporation of endothelial cells in vivo, IEEE Trans Ultrason Ferroelectr Freq Control, 61 (2014) 1661-1667.

全文公開日期本全文未授權公開 (校內網路)
全文公開日期本全文未授權公開 (校外網路)

簡易檢索 / 詳目顯示

相關論文