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Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e
| Section VIII. Chemotherapy of Neoplastic Diseases > |
Chapter 61. Cytotoxic Agents
Sections: Alkylating Agents and Platinum Coordination Complexes, Toxicities of Alkylating Agents, Clinical Pharmacology, Miscellaneous Alkylating Drugs, Platinum Coordination Complexes, II. Antimetabolites, Folic Acid Analogs, Pyrimidine Analogs, Cytidine Analogs, Purine Analogs, III. Natural Products, Microtubule-Damaging Agents, Vinca Alkaloids, Taxanes, Estramustine, Epothilones, Camptothecin Analogs, Antibiotics, Epipodophyllotoxins, Drugs of Diverse Mechanism of Action, Enzymes, Hydroxyurea, Differentiating Agents, Bibliography.
Topics Discussed: antineoplastic agents; cancer; cancer therapy; cancer treatment and chemotherapy; chemistry of antineoplastic agents; pharmacotherapy of oncologic disorders; therapy of neoplastic diseases.
Excerpt:"The pervasive toxic effects of sulfur mustard gas were noted as the result of its use in World War I. A potent vesicant, the gas caused a topical burn to skin, eyes, lungs, and mucosa and, after massive exposure, aplasia of the bone marrow and lymphoid tissue and ulceration of the GI tract. Early clinical experiments with topically applied sulfur mustard led to regression of penile tumors. Thereafter, Goodman, Gilman, the originators of this text, working with colleagues at Yale in a consortium organized by the U.S. Department of Defense, confirmed the antineoplastic action of the nitrogen mustards against a murine lymphoma. In 1942, they began clinical studies of intravenous nitrogen mustards in patients with lymphoma, launching the modern era of cancer chemotherapy (Gilman and Philips, 1946).The chemotherapeutic alkylating agents have in common the property of forming highly reactive carbonium ion intermediates. These reactive intermediates covalently link to sites of high electron density, such as phosphates, amines, sulfhydryl, and hydroxyl groups. Their chemotherapeutic and cytotoxic effects are directly related to the alkylation of reactive amines, oxygens, or phosphates on DNA. The N7 atom of guanine is particularly susceptible to the formation of a covalent..."
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