Neocarzinostatin: The Past, Present, and Future of Anticancer Drug

The 20th century has witnessed the great benefits of the development of antibi otics, which became a reality after World War IL More than 50 years ago I witnessed the miraculous therapeutic power of penicillin, when I was a student at the Tohoku University Medical School's Department of Bacteriology in Sendai, Japan. The late Dr. Kondo was a graduate student in the department at that time and developed the first crude penicillin preparation in Japan which was applied with dramatic results in two patients. Although there was patient-family consent at that time, ethics committees, randomization. mutagenesis tests, distribution studies, purity-criteria, and phar macokinetics were not yet in existence. Today, regulatory procedures have com plicated the whole drug-approval process. For example, any new antibiotics that have been proven effective in laboratory studies against gram-negative bacteria, as might exist in deadly plague bacteria, must still undergo a long and enormously costly regulatory process before they can be introduced to benefit society, and before government insurance can be applied. Chemical Structure of the Apoprotein of Neocarzinostatin.- Neocarzinostatin Chromophore: Structure and Mechanism of DNA Cleavage.- Synthesis and Chemistry of Nine-Membered Cyclic Enediyne Chromophores of Chromoprotein Antitumor Antibiotics.- Solution Structure of Neocarzinostatin Determined by Homonuclear Two-Dimensional Nuclear Magnetic Resonance.- Three-Dimensional Structure of Neocarzinostatin.- The Biochemical Mechanisms Involved in the Biological Effects Induced by Neocarzinostatin (NCS) and the NCS Chromophore.- Activation of Neocarzinostatin by NADPH Cytochrome P-450 Reductase: Proposal of an Ultimate Mode of Action in Cells Involving Oxygen Free Radicals.- Immunomodulating Antitumor Mechanisms of SMANCS.- Host-Mediated Antitumor Activity Induced by Neocarzinostatin and Its Polymer-Conjugated Derivative in Tumor-Bearing Mice.- Pharmacological Uniqueness and Clinical Effects of Neocarzinostatin.- Metamorphosis of Neocarzinostatin to SMANCS: Chemistry, Biology, Pharmacology, and Clinical Effect of the First Prototype Anticancer Polymer Therapeutic.- Supplementary Materials: Publications on Neocarzinostatin or Related Subjects, in English, 1960-1981.