| Introduction | xi | |
| Keynote Lecture | ||
| Mechanism of Action of Camptothecin | 1 | |
| Part I. | Mechanism of Action of Camptothecins | |
| Molecular and Biological Determinants of the Cytotoxic Actions of Camptothecins. Perspective for the Development of New Topoisomerase I Inhibitors | 11 | |
| Dependence of Anticancer Activity of Camptothecins on Maintaining Their Lactone Function | 27 | |
| Camptothecin Design and Delivery Approaches for Elevating Anti-Topoisomerase I Activities in Vivo | 36 | |
| Mechanisms of Resistance to Camptothecins | 46 | |
| Part II. | Mechanism-Based Design and Synthesis of Novel Camptothecins | |
| Structure-Based Analysis of the Effects of Camptothecin on the Activities of Human Topoisomerase I | 56 | |
| Mechanisms of DNA Topoisomerase I-Induced Cell Killing in the Yeast Saccharomyces cerevisiae | 65 | |
| Camptothecins as Probes of the Microenvironments of Topoisomerase I--DNA Complexes | 76 | |
| Part III. | Novel Topoisomerase I Inhibitors | |
| Preclinical and Clinical Trials of Topoisomerase Inhibitors | 92 | |
| Homocamptothecins: E-Ring Modified CPT Analogues | 100 | |
| The Cascade Radical Annulation Approach to New Analogues of Camptothecins. Combinatorial Synthesis of Silatecans and Homosilatecans | 112 | |
| Part IV. | New Camptothecin Derivatives and Formulations | |
| Structure-Activity Relationship of Alkyl Camptothecin Esters | 122 | |
| Conjugation of Camptothecins to Poly-(L-Glutamic Acid) | 136 | |
| 9-Nitrocamptothecin Liposome Aerosol Treatment of Human Cancer Subcutaneous Xenografts and Pulmonary Cancer Metastases in Mice | 151 | |
| Modified Lactone/Carboxylate Salt Equilibria in Vivo by Liposomal Delivery of 9-Nitro-Camptothecin | 164 | |
| New Analogues of Camptothecins. Activity and Resistance | 175 | |
| Intraperitoneal Topoisomerase-I Inhibitors. Preliminary Findings with 9-Aminocamptothecin | 178 | |
| Part V. | Pharmacology | |
| Transport of Topoisomerase I Inhibitors by the Breast Cancer Resistance Protein. Potential Clinical Implications | 188 | |
| Pharmacokinetics of Orally Administered Camptothecins | 195 | |
| Metabolism of CPT-11. Impact on Activity | 205 | |
| Pharmacology of Camptothecin Esters | 216 | |
| Part VI. | Clinical Trials I, Newer Analogues | |
| The Clinical Development of 9-Aminocamptothecin | 224 | |
| Alternative Administration of Camptothecin Analogues | 237 | |
| Topotecan (Hycamptin) and Topotecan-Containing Regimens in the Treatment of Hematologic Malignancies | 247 | |
| DX-8951f: Summary of Phase I Clinical Trials | 260 | |
| Part VII. | Clinical Trials II, Combination Therapy | |
| Cellular and Molecular Responses to Topoisomerase I Poisons. Exploiting Synergy for Improved Radiotherapy | 274 | |
| In Vitro Antitumor Activity of 9-Nitro-Camptothecin as a Single Agent and in Combination with other Antitumor Drugs | 293 | |
| p53 and p21 Are Major Cellular Determinants for DNA Topoisomerase I-Mediated Radiation Sensitization in Mammalian Cells | 298 | |
| Part VIII. | Poster Papers | |
| The Homocamptothecin, BN 80927, Is a Potent Topoisomerase I Poison and Topoisomerase II Catalytic Inhibitor 1 | 301 | |
| The Dual Topoisomerase Inhibitor, BN 80927, Is Highly Potent against Cell Proliferation and Tumor Growth | 303 | |
| Ubiquitin, SUMO-1, and UCRP in Camptothecin Sensitivity and Resistance | 306 | |
| A Spectrophotometric Study of the pH-Dependent and DNA Binding Properties of Topotecan | 309 | |
| Kinetics of in Vitro Hydrolysis of Homocamptothecins As Measured by Fluorescence | 314 | |
| The Combinatorial Synthesis of Racemic Homosilatecan Libraries via a Cascade Radical Annulation | 317 | |
| Combined Radiation and 9-Nitrocamptothecin (Rubitecan) in the Treatment of Locally Advanced Pancreatic Cancer | 320 | |
| Preclinical and Phase I Clinical Studies with Ckd-602, a Novel Camptothecin Derivative | 324 | |
| Action of Topoisomerase Targeting Drugs on Non-Hodgkin's Lymphoma and Leukemia. Correlation of Clinical and Cell Culture Studies | 326 | |
| Improvement of Therapeutic Index of Low-Dose Topotecan Delivered per os | 330 | |
| Camptothecin Dose, Schedule, and Timing of Administration for Clinical Radiation Sensitization | 334 | |
| Rapid Chromatin Reorganization Induced by Topoisomerase I-Mediated DNA Damage | 340 | |
| NF-[kappa]B Activation in Topoisomerase I Inhibitor-Induced Apoptotic Cell Death in Human Non-Small Cell Lung Cancer | 343 | |
| Phase I Study of 9-Nitro-20(s)-Camptothecin in Combination with Cisplatin for Patients with Advanced Malignancies | 345 | |
| Phase II Study of Intravenous DX-8951f in Patients with Advanced Ovarian, Tubal, or Peritoneal Cancer Refractory to Platinum, Taxane, and Topotecan | 349 | |
| Feasibility, Phase I, and Pharmacological Study of Aerosolized Liposomal 9-Nitro-20(S)-Camptothecin in Patients with Advanced Malignancies in the Lungs | 352 | |
| Inhibition of DNA Replication in Camptothecin-Treated Cells Is Regulated by Protein Kinases | 355 | |
| Part IX. | Concluding Remarks | |
| Concluding Remarks | 360 | |
| Index of Contributors | 361 |
