| Pharmacologic administration of interleukin-2. | |
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MedLine Citation:
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PMID: 20074271 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The development of biologic therapies for patients with cancer has in part been impeded by the extraordinary complexity and intrinsic feedback mechanisms promoting homeostasis in tissue injury, repair, inflammation, and immunity. Recombinant interleukin 2 (IL-2) therapy was initiated in 1984 based on its role as the prototypic T-cell growth factor, with novel roles deduced late after its FDA approval in regulating not only effector T cells but also regulatory T cells. Complicating its application, even in the most sophisticated centers, has been the manageable but difficult toxicities attendant on its use in spite of clear evidence of complete responses in 5-10% of treated patients with melanoma and renal cell carcinoma with extraordinary durability lasting now for almost 25 years, thus tantamount to "cures." Although efforts have been made to diminish toxicity or enhance efficacy the only substantive advance in combination therapy has been the application of tumor-infiltrating lymphocytes and the antibody to CTLA4. A deeper understanding of the "limiting" toxicity associated with mild flu-like symptoms and more debilitating cytokine "storm" not forthcoming. Here we propose the notion that the systemic syndrome associated with IL-2 administration is due to global cytokine-induced autophagy and temporally limited tissue dysfunction. The possible role of autophagy inhibitors to enhance efficacy and limit toxicity as well as possible problems with this approach are considered. |
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Authors:
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Antonio Romo de Vivar Chavez; William Buchser; Per H Basse; Xiaoyan Liang; Leonard J Appleman; Jodi K Maranchie; Herbert Zeh; Michael E de Vera; Michael T Lotze |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Annals of the New York Academy of Sciences Volume: 1182 ISSN: 1749-6632 ISO Abbreviation: Ann. N. Y. Acad. Sci. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2010-01-15 Completed Date: 2010-01-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7506858 Medline TA: Ann N Y Acad Sci Country: United States |
Other Details:
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Languages: eng Pagination: 14-27 Citation Subset: IM |
Affiliation:
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University of Pittsburgh Cancer Institute, Pennsylvania, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / administration & dosage, adverse effects, therapeutic use Autophagy / drug effects* Humans Interleukin-2 / administration & dosage, adverse effects*, metabolism, therapeutic use Neoplasms / diagnosis, drug therapy Prognosis |
| Grant Support | |
ID/Acronym/Agency:
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1 P01 CA 101944-04/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Interleukin-2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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