臺灣博碩士論文加值系統

光動力療法是結合了光感藥物及特定波長的光，應用於癌症的一種新療法。但光動力療法的光毒性 (phototoxicity)，會使患者必須要避光很長一段時間，造成患者生活上的不便。且光動力療法會使癌細胞產生血管內皮生長因子 (VEGF)，而血管內皮生長因子則是引起腫瘤血管新生，進而增加腫瘤的血流與轉移的可能性。

本論文分為兩部分，第一部份是利用雙極性高分子，包覆光感藥物Foscan，形成奈米微胞 (micelles)，並評估包覆光感藥物微胞的物理、化學性質、細胞毒性、光動力效果、抗腫瘤效果。

第二部分是結合光動力療法與抗血管新生療法 (anti-angiogenic therapy)，在使用光動力治療腫瘤後，給予可結合血管內皮生長因子的抗體-Avastin，去評估兩種藥物結合後對於抑制腫瘤生長與復發的效果。

本研究發現到PEOz-PLA雙極性高分子，為適合的光感藥物-Foscan載體，並在細胞實驗中，不照光的條件下並沒有毒性，而給光後仍有光動力的效果。而在評估光動力療法結合抗血管新生療法的研究中，我們發現此兩種療法結合後，有趨勢可以有效地抑制腫瘤生長與復發的現象。


關鍵字：光動力療法；抗血管新生療法；微胞；光感藥物；癌思停

Content
中文摘要…………………………………………………………………1
Abstract………..………………………………………………………...2

Part 1：Investigation of nanoparticles as photosensitizer carriers for photodynamic therapy
中文摘要…………………………………………………………………5
Abstract……..…………………………………………………………...6

1. Introduction……..…………………………………………………...8

2. Materials and Methods…….………………………………………12
2.1 Preparation of PEOz-PLA micelles…………………………….15
2.2 Loading Dose Analysis…………………………………………15
2.3 Particle Size Analysis…………………………………………..16
2.4 Cell culture…………………………………………………..…16
2.5 MTT assay……………………………………………………...16
2.6 Cytotoxicity Assay……………………………………………...17
2.7 Cellular Uptake…………………………………………………18
2.8 Fluorescence Microscopy………………………………………18
2.9 Intracellular localization by confocal laser scanning microscopy…………………………………………………...…19
2.10 Photodynamic Therapy in different drug concentrations….…...19
2.11 Photodynamic Therapy of different illumination time…………20
2.12 Animals and tumor model………………………………...……21
2.13 Animal assessment……………………………………………...22
2.14 PDT-related skin phototoxicity………………………..22

3. Results and Discussion……..………………………………………24
3.1 Dynamic Light Scattering Analysis…………………………….24
3.2 Loading Dose Analysis…………………………………………24
3.3 Cytotoxicity Assay in dark……………………………………...24
3.4 Cellular Uptake…………………………………………………25
3.5 Fluorescence Microscopy………………………………………25
3.6 Intracellular localization………………………………………..26
3.7 Photodynamic Therapy in different drug concentrations.……...26
3.8 Photodynamic Therapy of different illumination time…………27
3.9 Body weight loss in nude mice after PDT…………..…………28
3.10 PDT-related skin phototoxicity………………………..……....28
3.11 Anti-tumor effect of PDT in HT-29 solid tumors….………….29

4. Conclusion…..……………………………………………………...54

5. References……...…………………………………………………...56



Part 2：Photodynamic therapy alone or with anti-angiogenic therapy for colorectal cancer
中文摘要…….…………………………………………………………66
Abstract………………………………………………………………...67

1. Introduction……..…………………………………………………68

2. Materials and Methods……..……………………………………...72
2.1 Animals and tumor model…….………………………………..74
2.2 Light delivery……………….………………………………….74
2.3 Animal assessment………….………………………………….75

3. Results and Discussion……..……………………………………...76
3.1 Body weight loss in nude mice after treatments……………….76
3.2 Regrowth curves of HT-29 tumors after treatment…………….76
3.3 PDT-related skin phototoxicity………………………………...77
3.4 Individual regrowth curves of different groups………………..78
3.5 Survival curves of HT-29 tumors after treatment……………...79

4. Conclusion…………………………………………………………..88

5. References…………………………………………………………..90


Tables

Part 1：Investigation of nanoparticles as photosensitizer carriers for photodynamic therapy

Table 1 Pore cutoff size and effective permeability of tumor in mice.…12
Table 2 Grading system for skin phototoxicity………...……………….23
Table 3 Characterizations of Foscan-loaded micelles…………………..32
Table 4 P value of the Foscan-loaded micelles groups and the free Foscan groups in the same drug-light intervals……………...…………50


Part 2：Photodynamic therapy alone or with anti-angiogenic therapy for colorectal cancer

Table 1 P value of the different groups in the Kaplan-Meler curves…....87


Figures

Part 1：Investigation of nanoparticles as photosensitizer carriers for photodynamic therapy

Fig. 1 Electron micrographs of tumor vessels grew in mice…………....11
Fig. 2 Size distribution of Foscan-loaded micelles……………………..32
Fig. 3 Cytotoxicity study in different drug concentrations for Foscan-loaded micelles or free Foscan on HT-29 cells after incubation for 24 hours……………………...………………..….33
Fig. 4 Cellular uptake study of Foscan-loaded micelles or free Foscan on HT-29 cells……………..……………………………………...…34
Fig. 5 Fluorescence microscopic images of HT-29 cells incubated with Foscan-loaded micelles for different incubated time…………….35
Fig. 6 Fluorescence microscopic images of HT-29 cells incubated with free Foscan for different incubated time……………………....…36
Fig. 7 Intracellular localization of Foscan-loaded micelles in HT-29 cells observed by confocal laser scanning microscope…………..…....37
Fig. 8 Intracellular localization of free Foscan in HT-29 cells observed by confocal laser scanning microscope………………………..…….38
Fig. 9 Photodynamic effect in different drug concentrations for Foscan-loaded micelles or free Foscan on HT-29 cells…..……...39
Fig. 10 Photodynamic effect of Foscan-loaded micelles or free Foscan for different illumination time on HT-29 cells…………..…………40
Fig. 11 Body weight curves in nude mice after PDT…………………...41
Fig. 12 PDT-related skin phototoxicity……………….………………...42
Fig. 13 Skin phototoxicity in free Foscan 24 hours group……………...42
Fig. 14 Skin phototoxicity in Foscan-loaded micelles 24 hours group…………………………………………………………...44
Fig. 15 Skin phototoxicity in free Foscan 48 hours group…………………………………………………………...45
Fig. 16 Skin phototoxicity in Foscan-loaded micelles 48 hours group……………………………………………………………46
Fig. 17 Regrowth curves of HT-29 tumors…………………………...…47
Fig. 18 Regrowth curves of HT-29 tumors in the control group, the Foscan-loaded micelles 24 hours group and the free Foscan 24 hours group……………………………………………………..48
Fig. 19 Regrowth curves of HT-29 tumors in the control group, the Foscan-loaded micelles 48 hours group and the free Foscan 48 hours group…………………………………………………..…49
Fig. 20 PDT related skin overlying the tumor phototoxicity in the free Foscan 24 hours group………………………………………….50
Fig. 21 PDT related skin overlying the tumor phototoxicity in the Foscan-loaded micelles 24 hours group……………………..…51
Fig. 22 PDT related skin overlying the tumor phototoxicity in the free Foscan 48 hours group………………………………………….52
Fig. 23 PDT related skin overlying the tumor phototoxicity in the Foscan-loaded micelles 48 hours group…………………………………………………………....53


Part 2：Photodynamic therapy alone or with anti-angiogenic therapy for colorectal cancer

Fig. 1 Vessel normalization of tumors to antiangiogenic therapy.……..70
Fig. 2 Interactions between PDT and the tumor microenvironment…....71
Fig. 3 Body weight curves in mice after treatments…………………….81
Fig. 4 Regrowth curves of HT-29 tumors after treatments………...……82
Fig. 5 Pictures of the Control group…………………………………….83
Fig. 6 Pictures of the PDT only group………………………………..…83
Fig. 7 Pictures of the Avastin only group……………………………….84
Fig. 8 Pictures of the PDT+Avastin group……………………………...84
Fig. 9 Individual regrowth curves of the different groups……………....85
Fig. 10 Survival curves of HT-29 tumors after treatment……………….86

PART 1：Investigation of nanoparticles as photosensitizer carriers for photodynamic therapy
1.Kristan A. Keyes A Larry Mann A Karen Cox, Patti Treadway A Philip Iversen A Yun-Fei Chen, Beverly A. Teicher, Circulating angiogenic growth factor levels in mice bearing human tumors using Luminex Multiplex technology., Cancer Chemother Pharmacol 51 (2003) 321-327
2.Young D. Jung, Syed A. Ahmad, Yoshito Akagi, Yutaka Takahashi, Wenbiao Liu, Niels Reinmuth, Raymond M. Shaheen, Fan Fan, Lee M. Ellis, Role of the tumor microenvironment in mediating response to anti-angiogenic therapy., Cancer and Metastasis Reviews 19 (2000) 147-157
3.Harold F. Dvorak, Lawrence F. Brown, Michael Detmar, Ann M. Dvorak, Vascular Permeability Factor/Vascular Endothelial Growth Factor, Microvascular Hyperpermeability, and Angiogenesis., American Journal of Pathology 146 (1995) 1029-1035
4.DVORAK HF, NAGY JA, DVORAK JT, DVORAK AM, Identification and Characterization of the Blood Vessels of Solid Tumors That Are Leaky to Circulating Macromolecules., American Journal of Pathology 133 (1988) 95-105
5.SCHERPHOF G, ROERDINK F, DIJKSTRA J, ELLENS H, DEZANGER R, WISSE E, Uptake of Liposomes by Rat and Mouse Hepatocytes and Kupffer Cells. Biol. Cell 47 (1983) 47-58
6.M. Stubbs, Tumour pH, in: M. Molls, P. Vaupel (Eds.), Blood Perfusion and Microenvironment of Human Tumors: Implications for Clinical Radiooncology, Springer-Verlag, Berlin, 2000, pp. 113–120.
7.SUSAN K. HOBBS, WAYNE L. MONSKY, FAN YUAN, W.GREGORY ROBERTS, LINDA GRIFFITH, VLADIMIR P. TORCHILIN, RAKESH K. JAIN, Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment., Proc. Natl. Acad. Sci. 95 (1998) 4607-4612
8.YUAN F, DELLIAN M, FUKUMURA D, LEUNIG M, BERK DA, TORCHILIN VP, JAIN RK, Vascular Permeability in a Human Tumor Xenograft: Molecular Size Dependence and Cutoff Size., Cancer Research 55 (1995) 3752-3756
9.Annelies S.L. Derycke, Peter A.M. de Witte, Liposomes for photodynamic therapy., Advanced Drug Delivery Reviews 56 (2004) 17-30
10.Ging-Ho Hsiue, Chun-Hung Wang, Chun-Liang Lo, Chau-Hui Wang, Ju-Pi Li, Jia-Ling Yang, Environmental-sensitive micelles based on poly(2-ethyl-2-oxazoline)-b-poly(L-lactide) diblock copolymer for application in drug delivery., International Journal of Pharmaceutics 317 (2006) 69-75
11.Chau-Hui Wang, Chun-Hung Wang, Ging-Ho Hsiue, Polymeric micelles with a pH-responsive structure as intracellular drug carriers., Journal of Controlled Release 108 (2005) 140-149
12.Zhonggao Gao, Heidi D. Fain, Natalya Rapoport, Ultrasound-Enhanced Tumor Targeting of Polymeric Micellar Drug Carriers., Mol Pharm. 1 (2004) 317-330
13.Vladimir P. Torchilin, Structure and design of polymeric surfactant-based drugdelivery systems., Journal of Controlled Release 73 (2001) 137-172
14.Christine Allen , Jeannie Han , Yisong Yu , Dusica Maysinger , Adi Eisenberg, Polycaprolactone–b-poly(ethylene oxide) copolymer micelles as a delivery vehicle for dihydrotestosterone., Journal of Controlled Release 63 (2000) 275-286
15.G. Kwon, M. Naito, M. Yokoyama, T. Okano, Y.Sakurai, K. Kataoka, Block copolymer micelles for drug delivery: loading and release of doxorubicin., Journal of Controlled Release 48 (1997) 195-201
16.Glen S. Kwon, Teruo Okano, Polymeric micelles as new drug carriers., Advanced Drug Delivery Reviews 21 (1996) 107-116
17.Glen S. Kwon, Kazunori Kataoka, Block copolymer micelles as long-circulating drug vehicles., Advanced Drug Delivery Reviews 16 (1995) 295-309
18.J.M. Metselaar, E. Mastrobattista and G. Storm, Liposomes for Intravenous Drug Targeting: Design and Applications., Mini Reviews in Medicinal Chemistry 2 (2002) 319-329
19.Characterization of Shell Crosslinked Nanoparticles as a Drug Carrier for Photodynamic Therapy, 黃明怡, 2005, 碩士論文--國立臺灣大學醫學工程研究所
20.Thomas J. Dougherty, Charles J. Gomer, Barbara W. Henderson, Giulio Jori, David Kessel, Mladen Korbelik, Johan Moan, Qian Peng, Photodynamic Therapy., Journal of the National Cancer Institute 20 (1998) 889-905
21.Teiten MH, Bezdetnaya L, Merlin JL, Bour-Dill C, Pauly ME, Dicato M, Guillemin F, Effect of meta-tetra(hydroxyphenyl)chlorin (mTHPC)-mediated photodynamic therapy on sensitive and multidrug-resistant human breast cancer cells., J. Photochem. Photobiol. B: Biol. 62 (2001) 146-152
22.Melnikova VO, Bezdetnaya LN, Bour C, Festor E, Gramain MP, Merlin JL, Potapenko AY, Guillemin F, Subcellular localization of meta-tetra(hydroxyphenyl) chlorin in human tumor cells subjected to photodynamic treatment., J. Photochem. Photobiol. B: Biol. 49 (1999) 96-103
23.Xintao Shuai, Hua Ai, Norased Nasongkla, Saejeong Kim, Jinming Gao, Micellar carriers based on block copolymers of poly(ε-caprolactone) and poly(ethylene glycol) for doxorubicin delivery., Journal of Controlled Release 98 (2004) 415-426
24.S. Marchal, L. Bezdetnaya, F. Guillemin, Modality of Cell Death Induced by Foscan-Based Photodynamic Treatment in Human Colon Adenocarcinoma Cell Line HT29., Biochemistry (Moscow) 69 (2004) 45-49
25.Yaron Perry, M.D., Michael W. Epperly, Ph.D., Hiran C. Fernando, M.D., Ed Klein, M.D., Sid Finkelstein, M.D., Joel S. Greenberger, M.D., James D. Luketich, M.D., Photodynamic Therapy Induced Esophageal Stricture—An Animal Model: From Mouse to Pig., Journal of Surgical Research 123 (2005) 67-74
26.Yoshiharu Ninomiya, Yoshiyasu Itoh, Shingo Tajima, Akira Ishibashi, In vitro and in vivo expression of protoporphyrin IX induced by lipophilic 5-aminolevulinic acid derivatives., Journal of Dermatological Science 27 (2001) 114-120
27.Qian Peng, Trond Warloe, Johan Moan, Aslak Godal, Fabio Apricena, Karl-Erik Giercksky, Jahn M. Nesland, Antitumor Effect of 5-Aminolevulinic Acid-mediated Photodynamic Therapy Can Be Enhanced by the Use of a Low Dose of Photofrin in Human Tumor Xenografts., Cancer Research 61 (2001) 5824-5832
28.A Casas, AM del C Batlle, AR Butler, D Robertson, EH Brown, A MacRobert, PA Riley, Comparative effect of ALA derivatives on protoporphyrin IX production in human and rat skin organ cultures., British Journal of Cancer 80 (1999) 1525-1532
29.V. Kirveliene, G. Grazeliene, D. Dabkeviciene, I. Micke, D. Kirvelis, B. Juodka, J. Didziapetriene, Schedule-dependent interaction between Doxorubicin and mTHPC-mediated photodynamic therapy in murine hepatoma in vitro and in vivo., Cancer Chemother Pharmacol 57 (2006) 65-72
30.Martijn Triesscheijn, Marjan Ruevekamp, Maurice Aalders, Paul Baas, Fiona A. Stewart, Outcome of mTHPC Mediated Photodynamic Therapy is Primarily Determined by the Vascular Response., Photochemistry and Photobiology 81 (2005) 1161-1167
31.ESTELLE MAUGAIN, SIARHEI SASNOUSKI, VLADIMIR ZORIN, JEAN-LOUIS MERLIN, FRANCOIS GUILLEMIN, LINA BEZDETNAYA, Foscan-based photodynamic treatment in vivo: Correlation between efficacy and Foscan accumulation in tumor, plasma and leukocytes., Oncology Reports 12 (2004) 639-645
32.Ruth VEENHUIZEN, Hugo OPPELAAR, Marjan RUEVEKAMP, Jan SCHELLENS, Otilia DALESIO, Fiona STEWART, DOES TUMOUR UPTAKE OF FOSCAN DETERMINE PDT EFFICACY?, Int. J. Cancer 73 (1997) 236-239
33.P Cramers, M Ruevekamp, H Oppelaar, O Dalesio, P Baas, FA Stewart, Foscan uptake and tissue distribution in relation to photodynamic efficacy., British Journal of Cancer 88 (2003) 283-290
34.S Andrejevic Blant, TM Glanzmann, J-P Ballini, G Wagnie`res, H van den Bergh, P Monnier, Uptake and localisation of mTHPC (Foscan) and its14C-labelled form in normal and tumour tissues of the hamster squamous cell carcinoma model: a comparative study., British Journal of Cancer 87 (2002) 1470-1478
35.Vladislava O. MELNIKOVA, Lina N. BEZDETNAYA, Daniel BRAULT, Alexander Y. POTAPENKO, Franc¸ois GUILLEMIN, ENHANCEMENT OF META-TETRAHYDROXYPHENYLCHLORIN-SENSITIZED PHOTODYNAMIC TREATMENT ON HUMAN TUMOR XENOGRAFTS USING A WATER-SOLUBLE VITAMIN E ANALOGUE, TROLOX., Int. J. Cancer 88 (2000) 798-803
36.H-B Ris, T Krueger, A Giger, CK Lim, JCM Stewart, U Althaus, HJ Altermatt, Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts., British Journal of Cancer 79 (1999) 1061-1066
37.Veenhuizen RB, Ruevekamp MC, Oppelaar H, Helmerhorst TJM, Kenemans P, Stewart FA, Foscan-mediated photodynamic therapy for a peritoneal-cancer model: Drug distribution and efficacy studies., Int. J. Cancer 73 (1997) 230-235
38.Brett W. Engbrecht, Chandrakala Menon, Alexander V. Kachur, Stephen M. Hahn, and Douglas L. Fraker, Photofrin-mediated Photodynamic Therapy Induces Vascular Occlusion and Apoptosis in a Human Sarcoma Xenograft Model., Cancer Research 59 (1999) 4334-4342
39.Bourdon O, Laville I, Carrez D, Croisy A, Fedel P, Kasselouri A, Prognon P, Legrand P, Blais J, Biodistribution of meta-tetra( hydroxyphenyl)chlorin incorporated into surface-modified nanocapsules in tumor-bearing mice, PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES, 9 (2002) 709-714
40.Maeda N, Takeuchi Y, Takada M, Sadzuka Y, Namba Y, Oku N, Anti-neovascular therapy by use of tumor neovasculature-targeted long-circulating liposome, JOURNAL OF CONTROLLED RELEASE, 100 (2004) 41-52
41.Zalipsky S, Hansen CB, Oaks JM, Allen TM, Evaluation of blood clearance rates and biodistribution of poly(2-oxazoline)-grafted liposomes, JOURNAL OF PHARMACEUTICAL SCIENCES, 85 (1996) 133-137
42.GOMER CJ, FERRARIO A, TISSUE DISTRIBUTION AND PHOTOSENSITIZING PROPERTIES OF MONO-L-ASPARTYL CHLORIN-E6 IN A MOUSE-TUMOR MODEL, CANCER RESEARCH, 50 (1990) 3985-3990
43.Tran N, Krueger T, Pan Y, Yan H, Cheng C, Altermatt HJ, Ballini JP, Borle F, Ris HB, Andrejevic-Blant S, Correlation of photodynamic activity and fluorescence signaling for free and pegylated mTHPC in mesothelioma xenografts, LASERS IN SURGERY AND MEDICINE, 39 (2007) 237-244
44.Ferrario A, Chantrain CF, von Tiehl K, Buckley S, Rucker N, Shalinsky DR, Shimada H, DeClerck YA, Gomer CJ, The matrix metalloproteinase inhibitor prinomastat enhances photodynamic therapy responsiveness in a mouse tumor model, CANCER RESEARCH, 64 (2004) 2328-2332
45.Ferrario A, von Tiehl K, Wong S, Luna M, Gomer CJ, Cycloxygenase-2 inhibitor treatment enhances photodynamic therapy-mediated tumor response, CANCER RESEARCH, 62 (2002) 3956-3961
46.Konan-Kouakou YN, Boch R, Gurny R, Allemann E, In vitro and in vivo activities of verteporfin-loaded nanoparticles, JOURNAL OF CONTROLLED RELEASE, 103 (2005) 83-91

Part 2：Photodynamic therapy alone or with anti-angiogenic therapy for colorectal cancer
1.Kristan A. Keyes, Larry Mann, Karen Cox, Patti Treadway, Philip Iversen, Yun-Fei Chen, Beverly A. Teicher, Circulating angiogenic growth factor levels in mice bearing human tumors using Luminex Multiplex technology, Cancer Chemother Pharmacol 51 (2003) 321–327
2.Young D. Jung, Syed A. Ahmad, Yoshito Akagi, Yutaka Takahashi, Wenbiao Liu, Niels Reinmuth, Raymond M. Shaheen, Fan Fan1 and Lee M. Ellis, Role of the tumor microenvironment in mediating response to anti-angiogenic therapy, Cancer and Metastasis Reviews 19 (2000) 147–157
3.Rakesh K. Jain, Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy, Science 307 (2005) 58-62
4.K. Jin Kim, Bing Li, Jane Winer, Mark Armanini, Nancy Gillett, Heidi S. Phillips, Napoleone Ferrara, Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vitro, Nature 362 (1993) 841-844
5.Christopher J. Sweeney, Kathy D. Miller, George W. Sledge Jr, Resistance in the anti-angiogenic era: nay-saying or a word of caution?, TRENDS in Molecular Medicine 9 (2003) 24-29
6.Hans-Peter Gerber, Napoleone Ferrara, Pharmacology and Pharmacodynamics of Bevacizumab as Monotherapy or in Combination with Cytotoxic Therapy in Preclinical Studies, Cancer Research 65 (2005) 671-680
7.Maria Luisa Veronese, Peter J. O’Dwyer, Monoclonal antibodies in the treatment of colorectal cancer, European Journal of Cancer 40 (2004) 1292–1301
8.NAPOLEONE FERRARA, Vascular Endothelial Growth Factor as a Target for Anticancer Therapy, The Oncologist 9 (2004) 2-10
9.Nishan H. Fernando, Herbert I. Hurwitz, Inhibition of Vascular Endothelial Growth Factor in the Treatment of Colorectal Cancer, Seminars in Oncology 30 (2003) 39-50
10.Hong Jo Choi, Moon Soo Hyun, Ghap Joong Jung, Sang Soon Kim, Sook Hee Hong, Tumor Angiogenesis as a Prognostic Predictor in Colorectal Carcinoma with Special Reference to Mode of Metastasis and Recurrence, Oncology 55 (1998) 575–581
11.Tina Cascone, Teresa Troiani, Maria Pia Morelli, Cesare Gridelli, Fortunato Ciardiello, Antiangiogenic drugs in non-small cell lung cancer treatment, Current Opinion in Oncology 18 (2006) 151–155
12.Yaning Wang, David Fei, Martin Vanderlaan, An Song, Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro, Angiogenesis 7 (2004) 335-345
13.Ferrario A, Gomer CJ, Avastin enhances photodynamic therapy treatment of Kaposi''s sarcoma in a mouse tumor model, J. Environ. Pathol. Toxicol. Oncol. 25 (2006) 251-259
14.Alan Sandler, M.D., Robert Gray, Ph.D., Michael C. Perry, M.D., Julie Brahmer, M.D., Joan H. Schiller, M.D., Afshin Dowlati, M.D., Rogerio Lilenbaum, M.D., and David H. Johnson, M.D. Paclitaxel–Carboplatin Alone or with Bevacizumab for Non–Small-Cell Lung Cancer, New England Journal of Medicine, 355 (2007) 2542-2550
15.Charles J. Gomer, PhD, Angela Ferrario, PhD, Marian Luna, BS, Natalie Rucker, BS, Sam Wong, BS, Photodynamic Therapy: Combined Modality Approaches Targeting the Tumor Microenvironment, Lasers in Surgery and Medicine 38 (2006) 516–521
16.Nicolas Solban, PHD, Imran Rizvi, MS, Tayyaba Hasan, PhD, Targeted Photodynamic Therapy, Lasers in Surgery and Medicine 38 (2006) 522-531
17.SO Gollnick, SS Evans, H Baumann, B Owczarczak, P Maier, L Vaughan, WC Wang, E Unger, BW Henderson, Role of cytokines in photodynamic therapy-induced local and systemic inflammation, British Journal of Cancer 88 (2003) 1772-1779
18.Angela Ferrario, Anita M. Fisher, Natalie Rucker, Charles J. Gomer, Celecoxib and NS-398 Enhance Photodynamic Therapy by Increasing In vitro Apoptosis and Decreasing In vivo Inflammatory and Angiogenic Factors, Cancer Research 65 (2005) 9473-9478
19.Y.AKITA, K.KOZAKI, A.NAKAGAWA, T.SAITO, S.ITO, Y.TAMADA, S.FUJIWARA, N.NISHIKAWA, K.UCHIDA, K.YOSHIKAWA, T.NOGUCHI, O.MIYAISHI, K.SHIMOZATO, S.SAGA, Y.MATSUMOTO, Cyclooxygenase-2 is a possible target of treatment approach in conjunction with photodynamic therapy for various disorders in skin and oral cavity, British Journal of Dermatology 151 (2004) 472–480
20.Marcin Makowski, Tomasz Grzela, Justyna Niderla, Maciej Łazarczyk, Paweł Mro´z, Maciej Kopec´, Magdalena Legat, Katarzyna Strusin´ ska, Katarzyna Koziak, Dominika Nowis, Piotr Mro´wka, Maria Wa˛sik, Marek Jako´bisiak, Jakub Gołab, Inhibition of Cyclooxygenase-2 Indirectly Potentiates Antitumor Effects of Photodynamic Therapy in Mice, Clinical Cancer Research 9 (2003) 5417-5422
21.Angela Ferrario, Karl F. von Tiehl, Natalie Rucker, Margaret A. Schwarz, Parkash S. Gill, Charles J. Gomer, Antiangiogenic Treatment Enhances Photodynamic Therapy Responsiveness in a Mouse Mammary Carcinoma, Cancer Research 60 (2000) 4066-4069
22.Angela Ferrario, Christophe F. Chantrain, Karl von Tiehl, Sue Buckley, Natalie Rucker, David R. Shalinsky, Hiroyuki Shimada, Yves A. DeClerck, Charles J. Gomer, The Matrix Metalloproteinase Inhibitor Prinomastat Enhances Photodynamic Therapy Responsiveness in a Mouse Tumor Model, Cancer Research 64 (2004) 2328-2332
23.Angela Ferrario, Karl von Tiehl, Sam Wong, Marian Luna, Charles J. Gomer, Cyclooxygenase-2 Inhibitor Treatment Enhances Photodynamic Therapy-mediated Tumor Response, Cancer Research 62 (2002) 3956-3961