by Ho King Wah Stephen. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 251-304). / Title Page --- p.1 / Table of Contents --- p.2 / Summary --- p.3 / Glossary of abbreviations used in the thesis --- p.10 / List of Figures --- p.12 / List of Tables --- p.20 / Acknowledgments --- p.24 / Chapter Chapter 1 --- Hepatic Cancer - Review of the Medical Literature --- p.25 / Chapter Chapter 2 --- Selective Internal Radiation Therapy - Review of the Medical Literature --- p.47 / Chapter Chapter 3 --- The Background In Physics --- p.76 / Chapter Chapter 4 --- Hypothesis and Testing the Hypothesis --- p.88 / Chapter Chapter 5 --- Parameters Required in the Partition Model --- p.98 / Chapter Chapter 6 --- Prediction of Radiation Dose and Verification of the Partition Model --- p.143 / Chapter Chapter 7 --- Clinical Evaluation of the Partition Model --- p.181 / Chapter Chapter 8 --- Conclusions and Future Development --- p.248 / References --- p.251

丹參為雙子葉植物唇形科鼠尾草族植物的乾燥根及根莖。在中國，丹參為廣泛用於治療心血管疾病的藥用植物，而在西方，丹參也常作為一種輔助性藥物。《中國藥典2010版》收錄了35個以上含有丹參的複方或者方劑。在這些複方中，採用了富含丹酚酸和丹參酮的丹參水提物、乙醇提取物或兩者的混合物。丹參提取物具有較強的抗氧化作用，被認為在化學預防和化療的輔助治療中有一定用途。作為主要的丹參水溶性成分，熱敏感的丹酚酸在提取與加熱過程中可能會降解為其他丹酚酸。丹參水提取物的化學組成可能會在不同熱水提取溫度下有所不同，進而影響其藥理活性。在本研究中，通過加熱回流提取和在不同溫度下的微波提取（MAE-W）獲得了6種丹參水提取物，並對這些提取物進行化學成分和藥理分析，考察它們的抗氧化、抗凋亡和血管舒張作用。在這些提取物中，第三輪的微波提取物（100 oC）含有最多的丹酚酸和丹參酮，在1，1-二苯基-2-三硝基苯肼（DPPH）法和鐵還原/抗氧化能力（FRAP）法中具有最強的抗氧化活性，在2,2'-偶氮二(2-脒基丙烷)二鹽酸鹽（AAPH）誘導人血紅細胞的溶血實驗和過氧化氫誘導大鼠心肌細胞H9c2凋亡實驗中還顯示了最強的抑制作用，對大鼠腦基底動脈有最強的鬆弛效應。這些丹參水提取物的抗氧化作用與它們的血管舒張效應呈一定的線性關係（回歸係數r = 0.895 - 0.977）。通過多元線性回歸分析發現，丹參素可以作為丹參水提物的抗氧化和血管舒張功能的顯著性標記物，而丹參酮IIA則是抑制過氧化氫誘導大鼠心肌H9c2細胞凋亡的標記物。 / 作為丹參中主要的脂溶性成分，丹參酮在不同的腫瘤細胞系和荷瘤小鼠模型中展示了抗癌潛力。這些丹參酮的抗癌機制包括細胞週期阻滯，觸發半胱天冬酶（Caspase）依賴的內源性和外源性的凋亡途徑和絲裂原激活的蛋白激酶（MAPK）信號通路等。丹參新酮（miltirone）是從丹參中分離得到的松香烷型二萜醌類化合物，具有多種的藥理活性，如抗氧化，抗焦慮和抗腫瘤等。本研究評估了丹參新酮在人肝癌HepG2細胞系和P-糖蛋白（P-gp）過表達的阿霉素耐藥HepG2細胞系（R-HepG2）中的凋亡作用及其機制。丹參新酮在HepG2細胞中顯示了細胞毒性（EC₅₀值為7.06 微摩），而丹參新酮在抑制HepG2和R-HepG2細胞增殖中的濃度依賴性沒有顯著性差異。丹參新酮（1.56 - 6.25微摩）與阿霉素（DOX）對R-HepG2細胞的增殖具有協同效應，在達到50的生長抑制時，它們的聯合用藥指數為0.3至0.5。流式細胞術分析表明，丹參新酮降低了R-HepG2細胞中P-gp介導的阿霉素外排，分子對接研究表明該效果是通過抑制P-gp的藥物結合位點。在非壞死濃度（25微摩或以下），丹參新酮在HepG2和R-HepG2細胞中活化了Caspase依賴的凋亡途徑，誘導產生活性氧（ROS）和氧化應激，且觸發ROS介導的包括p38 MAPK，應激活化蛋白激酶/c-Jun氨基末端激酶（SAPK / JNK）以及細胞外調節激酶1和2在內的MAPK信號通路。綜上所述，在R-HepG2中丹參新酮是P-gp和細胞增殖的雙重抑制劑，顯示了其在治療肝癌（HCC）的潛力。 / 為了增加藥物開發的成功率，在藥物發現的早期階段應考察新化學實體（NCEs）的蛋白結合率，清除率，藥動學參數，以及藥物代謝相互作用等體內代謝參數。以往的研究已經顯示了從丹參中分離得到的四種主要丹參酮對人和大鼠的細胞色素P450酶介導的探針底物的代謝具有不同程度的抑制作用，需要注意丹參和其他藥物間的相互作用。本研究的另一目的是在人類肝微粒體中探討丹參新酮與探針底物間的細胞色素P450酶介導的代謝相關的相互作用。人肝微粒體孵育實驗結果表明丹參新酮對CYP1A2（IC₅₀值為 1.73微摩）和CYP2C9（IC₅₀值為8.61微摩）有中等強度的抑制，對CYP2D6（IC₅₀值為30.20微摩）和CYP3A4（IC₅₀值為33.88微摩）有弱的抑制。酶動力學和分子對接研究的結果進一步表明，丹參新酮為CYP1A2（Ki值為3.17微摩）的中等強度混合型抑制劑，是CYP2C9（Ki值為1.48微摩）的中等強度競爭型抑制劑，也是CYP2D6（Ki值為24.25微摩）和CYP3A4（Ki值為35.09微摩）的弱的混合型抑制劑。這些結果表明，應考慮丹參新酮與CYP1A2和CYP2C9代謝的藥物間的相互作用，但是可認為其與CYP2D6及CYP3A4代謝的藥物間幾乎不存在相互作用。 / 總之，本研究考察了不同提取方法對丹參提取物成份及其藥效的影響，確定了不同用途的丹參提取物的質控標記物。本研究還考察了丹參新酮體外抗肝癌的能力及其藥物代謝相互作用為基礎的類藥性,為其進一步的體內試驗提供了依據。 / Danshen, the dried root and rhizome of Salvia miltiorrhiza Bg. (Fam. Labiatae), is a widely used medicinal plant for the treatment of cardiovascular diseases in China and also a complementary medicine in the West. Danshen is indexed in the Pharmacopoeia of People’s Republic of China (2010 Edition), with more than 35 formulations and concoctions containing Danshen water-extracts, ethanolic extracts or their combination which are rich in phenolic acids and tanshinones with various contents. Danshen extracts have been considered for the use as an adjunct in chemoprevention and chemotherapy due to their strong antioxidant effects. Phenolic acids, the major water-soluble components in Danshen, are thermosensitive and may degrade to other phenolic acids during extractions upon heating. The chemical profiles of Danshen water-extracts may vary with different heat water extraction at different temperatures, affecting the composition and bioactivity of the extracts obtained. In this study, six water-extracts of Danshen obtained from heat reflux water extraction and microwave-assisted extraction with water (MAE-W) at different temperatures were prepared for evaluation of their composition and pharmacological effects such as antioxidant, anti-apoptosis and vascular relaxation. Among these extracts obtained, the third-round MAE-W (100 °C) product, which was the last round product obtained by extracting the same crude material three times, had the highest contents of phenolic acids and tanshinones, with the strongest antioxidant activity estimated by 2, 2-diphenyl-1-(2, 4, 6-trinitrophenyl) hydrazyl (DPPH) assay and ferric reducing / antioxidant potential (FRAP) assay. This extract also possessed the strongest inhibitory effects on 2, 2'-azobis-2-amidino-propane (AAPH)-induced haemolysis in human red blood cells, hydrogen peroxide-induced apoptosis in rat heart H9c2 cells and the highest relaxation effects on rat basilar artery. The antioxidant effects of Danshen water-extracts linearly correlated to their relaxation effects (r = 0.895 to 0.977). Through multiple linear regression analysis, danshensu was found to be the most significant marker in the antioxidant and vasodilation effects of Danshen water-extract, while tanshinone IIA as the marker on hydrogen peroxide-induced apoptosis in rat heart H9c2 cells. Danshensu is, therefore, a useful marker for the quality control of Danshen water-extracts in antioxidant and vasodilation, while tanshinone IIA for anti-apoptotic potential of water-extracts. / Tanshinones, the major lipid-soluble components isolated from Danshen, have been reported for their anti-cancer potential in various cell lines and tumor-bearing mice models. Their anti-cancer mechanisms are also well-studied, mainly through cell cycle arrest, caspase-dependent apoptotic pathways and mitogen activated protein kinase (MAPK) signaling pathways. Miltirone, another abietane type-diterpene quinone isolated from Danshen, has been reported for its anti-oxidative, anxiolytic and anti-cancer effects. This study evaluated the apoptotic effect of miltirone and the underlying mechanisms in a human hepatoma HepG2 cell line and its p-glycoprotein (P-gp)-overexpressed doxorubicin-resistant counterpart (R-HepG2). Miltirone showed similar cytotoxicity in HepG2 (EC₅₀ = 7.06 μM) and R-HepG2 (EC₅₀ = 12.0 μM), demonstrated synergistic effects (1.56 - 6.25 μM) with doxorubicin (DOX) on the growth inhibition of R-HepG2 (synergism: 0.3 < CI < 0.5 at 50 % inhibition). Flow cytometric analysis showed that miltirone decreased P-gp-mediated DOX efflux in R-HepG2, and molecular docking studies illustrated that this effect was through inhibition on the active site of P-gp. At non-necrotic concentrations (25 μM or below), miltirone activated caspase-dependent apoptotic pathways, and induced the generation of reactive oxygen species (ROS) and oxidative stress which triggered ROS-mediated MAPK signaling pathways, including p38 MAPK, stress-activated protein kinase / c-Jun N-terminal kinase (SAPK/JNK) and extracellular regulated kinase 1/2, in both HepG2 and R-HepG2 cells. It is therefore concluded that miltirone is a dual inhibitor on P-gp and cell proliferation in R-HepG2 cells, with potential for the treatment of human hepatocellular carcinoma (HCC). / In order to improve the successful rates in drug development, the in vivo metabolic parameters of new chemical entities (NCEs), such as protein bindings, clearance rate, pharmacokinetic parameters and metabolism-based drug-drug interactions, should be considered at the early stage of drug discovery. Previous studies have shown that major tanshinones isolated from Danshen inhibited the metabolism of model probe substrates of human and rat CYP450 enzymes, with potential in causing herb-drug interactions. The aim of this study was to study the effect of miltirone on the metabolism of model probe substrates of CYP1A2, 2C9, 2D6 and 3A4 in pooled human liver microsomes. Miltirone showed moderate inhibition on CYP1A2 (IC₅₀ = 1.73 μM) and CYP2C9 (IC₅₀ = 8.61 μM), and weak inhibition on CYP2D6 (IC₅₀ = 30.20 μM) and CYP3A4 (IC₅₀ = 33.88 μM). Enzyme kinetic studies showed that miltirone competitively inhibited CYP2C9 (Ki = 1.48 μM), and displayed mixed type inhibitions on CYP1A2, CYP2D6 and CYP3A4 with Ki values of 3.17 μM, 24.25 μM and 35.09 μM, respectively. Molecular docking study further confirmed the ligand-binding conformations of miltirone in the active sites of human CYP450 isoforms. These findings suggested that miltirone may have potential drug-drug interactions with CYP1A2- and CYP2C9-metabolized drugs, and to a lesser extent with CYP2D6- and CYP3A4-metabolized drugs. / In conclusion, this study investigated the effects of Danshen water-extracts produced by different extraction methods on the chemical compositions and pharmacological activities, and consequently confirmed the biomarkers for the quality control of Danshen water-extracts for different medicinal uses. This study also demonstrated the anti-cancer potential of miltirone for HCC in vitro and the metabolism-based drug-drug interactions for its drug-likeness, which may provide useful and promising data for in vivo anti-cancer study of miltirone and further pre-clinical studies. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Zhou, Xuelin / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 195-224). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Abstract --- p.i / 論文摘要 --- p.v / Publications based on the work in this thesis --- p.viii / Acknowledgements --- p.x / Abbreviations --- p.xii / Table of Contents --- p.xv / Chapter Chapter 1 --- General introduction --- p.1 / Chapter 1.1 --- Reactive oxygen species and carcinogenesis --- p.1 / Chapter 1.2 --- Reactive oxygen species and tumor progression & metastasis --- p.2 / Chapter 1.3 --- Antioxidant enzymes in chemoprevention and chemotherapy --- p.3 / Chapter 1.3.1 --- Glutathione and Glutathione reductase --- p.5 / Chapter 1.3.2 --- Glutathione Peroxidase --- p.5 / Chapter 1.3.3 --- Glutathione S-transferases --- p.6 / Chapter 1.3.4 --- NAD(P)H: quinone reductase 1 --- p.7 / Chapter 1.3.5 --- Heme oxygenase-1 --- p.8 / Chapter 1.3.6 --- Thioredoxin reductase --- p.9 / Chapter 1.3.7 --- Superoxide Dismutase --- p.10 / Chapter 1.3.8 --- Catalase --- p.11 / Chapter 1.4 --- Medicinal uses of Danshen --- p.12 / Chapter 1.5 --- Analysis of Danshen and its components --- p.14 / Chapter 1.6 --- Antioxidant effects of Danshen extract and its bioactive compounds in chemoprevention and chemotherapy-related disease --- p.19 / Chapter 1.7 --- Anti-cancer effects of tanshinones isolated from Danshen --- p.21 / Chapter 1.7.1 --- Tanshinone IIA --- p.22 / Chapter 1.7.2 --- Tanshinone I --- p.26 / Chapter 1.7.3 --- Cryptotanshinone --- p.27 / Chapter 1.7.4 --- Dihydrotanshinone --- p.27 / Chapter 1.8 --- Metabolism / disposition of Danshen and its major active ingredients --- p.28 / Chapter 1.9 --- Herb-drug interactions with Danshen --- p.31 / Chapter 1.10 --- Effects of Danshen (and its major active ingredients) on model probe substrates of CYP isoforms --- p.33 / Chapter 1.11 --- CYPs induction by Danshen and its active components --- p.38 / Chapter 1.12 --- Effects of Danshen / active ingredients on drug transporter proteins --- p.40 / Chapter 1.13 --- CYP450 inhibition screening for new chemical entity --- p.42 / Chapter 1.14 --- Molecular docking analysis --- p.44 / Chapter 1.15 --- The Aim of this study --- p.45 / Chapter Chapter 2 --- Quantitative and qualitative studies to evaluate the efficiency of different heat water-extractions --- p.48 / Chapter 2.1 --- Introduction --- p.48 / Chapter 2.2 --- Materials and methods --- p.51 / Chapter 2.2.1 --- Materials and apparatus --- p.51 / Chapter 2.2.2 --- Extraction procedures --- p.51 / Chapter 2.2.3 --- HPLC analysis --- p.54 / Chapter 2.2.4 --- DPPH assay and FRAP assay --- p.54 / Chapter 2.2.5 --- Inhibition of 2,2'-azobis-2-amidinopropane (AAPH)-induced haemolysis in human red blood cells --- p.55 / Chapter 2.2.6 --- Protective effects on hydrogen peroxide-induced apoptosis in rat heart H9c2 cells --- p.56 / Chapter 2.2.7 --- Vasodilation effects on rat basilar artery --- p.57 / Chapter 2.2.8 --- Statistical analysis --- p.58 / Chapter 2.3 --- Results and Discussion --- p.59 / Chapter 2.3.1 --- Chemical profiles analyzed by HPLC analysis --- p.59 / Chapter 2.3.2 --- DPPH assay and FRAP assay --- p.63 / Chapter 2.3.3 --- Inhibition of AAPH-induced haemolysis --- p.65 / Chapter 2.3.4 --- Protective effects on hydrogen peroxide-induced apoptosis --- p.69 / Chapter 2.3.5 --- Vasodilation effects on rat basilar artery --- p.71 / Chapter 2.3.6 --- Multiple linear regression analysis --- p.76 / Chapter Chapter 3 --- Effects of miltirone on cell proliferation in a hepatoma HepG2 cell line and its doxorubicin-resistant counterpart --- p.83 / Chapter 3.1 --- Introduction --- p.83 / Chapter 3.2 --- Materials and Methods --- p.87 / Chapter 3.2.1 --- Chemicals --- p.87 / Chapter 3.2.2 --- Cell culture --- p.87 / Chapter 3.2.3 --- Cell viability test --- p.88 / Chapter 3.2.4 --- Drug-efflux study by flow cytometry --- p.89 / Chapter 3.2.5 --- Molecular docking study and Ligand-based prediction --- p.90 / Chapter 3.2.6 --- Measurement of ROS generation by confocal microscopy and flow cytometry --- p.91 / Chapter 3.2.7 --- GSH and GSSG determination for oxidative stress --- p.93 / Chapter 3.2.8 --- Apoptosis-related proteins expression detected by Western blotting analysis --- p.94 / Chapter 3.2.9 --- Data analysis --- p.96 / Chapter 3.3 --- Results --- p.97 / Chapter 3.3.1 --- Cytotoxicity in hepatoma cells --- p.97 / Chapter 3.3.2 --- Drug-efflux study by flow cytometry --- p.104 / Chapter 3.3.3 --- Molecular docking study and Ligand-based prediction --- p.108 / Chapter 3.3.4 --- ROS generation --- p.113 / Chapter 3.3.5 --- Determination of GSH/GSSG ratio --- p.117 / Chapter 3.3.6 --- Caspase-dependent apoptosis. --- p.121 / Chapter 3.3.7 --- Phosphorylation of MAPKs --- p.126 / Chapter 3.4 --- Discussion --- p.134 / Chapter Chapter 4 --- Enzyme kinetic and molecular docking studies of miltirone on major human cytochrome P450 isozymes inhibitions --- p.139 / Chapter 4.1 --- Introduction --- p.139 / Chapter 4.2 --- Material and Methods --- p.141 / Chapter 4.2.1 --- Materials and Reagents --- p.141 / Chapter 4.2.2 --- Incubation conditions --- p.142 / Chapter 4.2.3 --- Samples preparation --- p.143 / Chapter 4.2.4 --- HPLC analysis --- p.143 / Chapter 4.2.5 --- CYP inhibition and enzymatic kinetic study --- p.144 / Chapter 4.2.6 --- Molecular docking analysis --- p.145 / Chapter 4.2.7 --- Data analysis --- p.146 / Chapter 4.3 --- Results --- p.148 / Chapter 4.3.1 --- CYP inhibition and enzymatic kinetic study --- p.148 / Chapter 4.3.2 --- Molecular docking study of miltirone --- p.167 / Chapter 4.4 --- Discussions --- p.184 / Chapter Chapter 5 --- General discussion --- p.188 / References --- p.195

Leung, Ching Hei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 101-110). / Abstracts in English and Chinese. / Acknowledgements --- p.i / 摘要（Abstract in Chinese) --- p.iii / Abstract --- p.v / List of Abbreviations --- p.vii / List of Figures and Tables --- p.ix / Table of Content --- p.xi / Chapter CHAPTER 1 --- Introduction / Chapter 1.1 --- History and development of photodynamic therapy --- p.1 / Chapter 1.2 --- Basic principle of photodynamic therapy: the beauty of the treatment --- p.3 / Chapter 1.3 --- "Photosensitizers: From discovery, synthesis to modifications" --- p.6 / Chapter 1.4 --- Enhancement of selective retention of PS in cancerous tissue --- p.10 / Chapter 1.5 --- Development of silicon (IV) phthalocyanine derivatives --- p.14 / Chapter 1.6 --- Death mechanisms in photodynamic therapy --- p.17 / Chapter 1.7 --- Objectives of the present study --- p.18 / Chapter CHAPTER 2 --- Materials and Methods / Chapter 2.1 --- Synthesis of BAM-SiPc --- p.20 / Chapter 2.2 --- Preparation of BAM-SiPc solution for photodynamic treatment --- p.20 / Chapter 2.3 --- Cell line and culture conditions --- p.21 / Chapter 2.4 --- Animal tumor model --- p.23 / Chapter 2.5 --- PDT laser source --- p.23 / Chapter 2.6 --- In vitro photodynamic activity assay --- p.23 / Chapter 2.6.1 --- Preparation of cells for photodynamic treatment / Chapter 2.6.2 --- In vitro photodynamic treatment / Chapter 2.6.3 --- Cell viability assay / Chapter 2.7 --- "Determination of reactive oxygen species production by 2',7'- dichlorofluorescein diacetate (DCFDA) assay" --- p.28 / Chapter 2.8 --- Analysis of cell cycle arrest --- p.28 / Chapter 2.9 --- Biodistribution of BAM-SiPc --- p.29 / Chapter 2.10 --- In vivo photodynamic treatment --- p.30 / Chapter 2.11 --- Assay for plasma enzyme activities --- p.30 / Chapter 2.12 --- Determination of cellular uptake of BAM-SiPc --- p.31 / Chapter 2.13 --- Metabolism of BAM-SiPc --- p.31 / Chapter 2.14 --- Histochemical staining --- p.32 / Chapter 2.14.1 --- Preparation of paraffin-embedded tissue section / Chapter 2.14.2 --- Haematoxylin and Eosin (H & E) staining / Chapter 2.14.3 --- Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay / Chapter 2.15 --- Conjugation of BAM-SiPc with LDL --- p.34 / Chapter 2.15.1 --- Analysis of the phototoxicity and cellular uptake of BAM- SiPc in the presence of LDL / Chapter 2.15.2 --- Gel filtration analysis of the mixture of LDL and BAM- SiPc / Chapter 2.16 --- Statistical analysis --- p.35 / Chapter CHAPTER 3 --- Results / Chapter 3.1 --- In vitro photodynamic activity assays --- p.36 / Chapter 3.2 --- Tissue distribution of BAM-SiPc in HepG2- bearing nude mice --- p.39 / Chapter 3.3 --- Anti-tumor activities of in vivo PDT with BAM-SiPc --- p.42 / Chapter 3.3.1 --- In vivo effect of PDT treatment with BAM-SiPc on HepG2 and HT29 tumor growth / Chapter 3.3.2 --- Dosage effect on anti-tumor activities by BAM-SiPc mediated PDT / Chapter 3.4 --- Analysis of intrinsic toxicity induced by BAM-SiPc mediated PDT --- p.48 / Chapter 3.4.1 --- H & E staining of liver sections of nude mice after in vivo PDT / Chapter 3.4.2 --- Plasma enzyme activity assays of PDT treated mice / Chapter 3.5 --- BAM-SiPc metabolism in in vitro culture cells and liver homogenate --- p.53 / Chapter 3.5.1 --- Cellular uptake of BAM-SiPc / Chapter 3.5.2 --- BAM-SiPc metabolism in cultured normal liver cells and cancer cells / Chapter 3.5.3 --- BAM-SiPc metabolism by mice liver homogenate / Chapter 3.6 --- Death mechanism induced by BAM-SiPc mediated PDT --- p.62 / Chapter 3.6.1 --- Events related to cell death induced by in vitro BAM-SiPc mediated PDT / Chapter 3.6.2 --- Death mechanism exerted by in vivo BAM-SiPc mediated PDT / Chapter 3.7 --- Effect on phototoxicity of BAM-SiPc in the presence of LDL --- p.70 / Chapter 3.7.1 --- Effect on phototoxicity of BAM-SiPc after mixing BAM- SiPc with LDL / Chapter 3.7.2 --- Gel filtration for analysis of the LDL-BAM-SiPc mixture / Chapter CHAPTER 4 --- Discussion / Chapter 4.1 --- Anti-cancer effect of BAM-SiPc on different cancer cell lines --- p.76 / Chapter 4.2 --- Tissue distribution of BAM-SiPc in HepG2 bearing nude mice --- p.77 / Chapter 4.3 --- In vivo effect of BAM-SiPc mediated PDT on HepG2 and HT29 tumor growth --- p.80 / Chapter 4.4 --- Analysis of the safety of using BAM-SiPc as a potential agent in PDT --- p.83 / Chapter 4.5 --- Metabolism of BAM-SiPc --- p.84 / Chapter 4.6 --- Mechanism of the apoptosis triggered by BAM-SiPc mediated PDT --- p.88 / Chapter 4.7 --- Death mechanism induced by in vivo PDT with BAM-SiPc --- p.93 / Chapter 4.8 --- Phototoxicity of BAM-SiPc in the presence of LDL --- p.94 / Chapter CHAPTER 5 --- Conclusion and Future perspective / Chapter 5.1 --- Conclusion --- p.97 / Chapter 5.2 --- Future perspective --- p.98 / References